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Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/anatomichistoloOOoert 


PLATE  1. 


(Jortflx 


Bcundary 
Zone 


PyraTiiid 


Papilla 


Structures  of  the  Normal  Kidney. 

1,  Capsule;  2,  convoluted  tubule;  3,  outer  layer  of  the  capsule;  4,  intervening  space; 
5,  reflected  portion  of  the  capsule;  6,  distal  convoluted  tubule;  7,  irregular  portion  of 
distal  convoluted  tubule;  8,  end  portion  of  distal  convoluted  tubule;  9,  collecting 
tubule;  10,  ascending  loop  of  Menle;  11,  arteria  recta;  12,  vena  recta;  13,  loop  of 
Henle;  14,  pyramid;  15,  papilla;  16,  papillary  vascular  plexus;  17,  main  collecting 
tubule;  18,  calix;  19,  boundary  zone;  20,  larger  branch  of  renal  vein;  21,  larger  branch 
of  renal  artery;  22,  descending  loop  of  Hcnlo;  23,  interlobular  vein,  collocting  from  the 
stellate  plexus;  24,  narrow  portion  of  ascending  loop  of  TTenle;  25,  interlobular  vein; 
26,  interloVnilar  artery;  27,  glomerular  capillary  network;  28,  stellate  plexus  of  capil- 
laries; 29,  efferent  vessel;  30,  afferent  vessel. 


THE    ANATOMIC 
HISTOLOGICAL    PROCESSES 


OF 


BRIGHT'S  DISEASE 

AND  THKIR   RKLATION  TO  THE  FUNCTIONAL  CHANGES 


LECTURES    DELIVERED    IN    THE 

RUSSELL    SAGE    INSTITUTE    OF    PATHOLOGY 

CITY    HOSPITAL,    NEW    YORK 
During  the  Wintkr   of    1909 


BY 

HORST  OERTEL 

niRECTOR    OF     THE     RUSSELL    SAOE     INSTITUTE    OF     PATHOLOfi  V ,     NEW     YORK 


I  L  L  i'S  TRJTED 


PHILADELPHIA    AND    LONDON 

W.    B.    SAUNDERS    COMPANY 

1910 


Copyright,  1910,  by  W,  B.  Saunders  Company 


PRINTED    I.V    AMERICA 


TO 

EDWARD  G.  JANEWAY 

TO  WHOM  THE  SCIENTIFIC  PHACTICE  OF  MEDICINE  IN  .VMEKICA 
OWES  A  HEAVY  DEUr.   AND  WHOSE  METHODS,    WORK 
AND  ACCOMPLISHME.Vl-S  HAVE  AT  ALL  TIMES 
BEEN    EXAMPLE.  AID.  AND    INSPIRA- 
TION,   IN    LASTING    GRATITUDE 


PREFACE 


These  lectures  were  delivered  at  the  request  of  the  Resident 
Staff  of  the  New  York  City  Hospital  in  the  Russell  Sage  In- 
stitute of  Pathology,  during  the  winter  semester  1908  to  1909 
before  an  audience  of  recent  graduates  and  some  advanced  under- 
graduates in  medicine.  My  hearers  wished  to  o])tain  in  syste- 
matic and  connected  form  the  almost  daily  experience  in  hospital 
and  pathological  institute.  They  wanted  primarily  to  intelli- 
gently understand  what  they  saw  at  the  bedside  and  at  the 
autopsy  tal3le. 

The  lectures  deal,  therefore,  with  the  morphology  of  nephritis, 
and  in  a  somewhat  different  form  from  the  usual  manner.  Ever}^- 
where  I  have  endeavored  to  particularly  emphasize  relations 
and  to  reconstruct  the  whole  as  a  unit  of  interwoven  processes, 
rather  than  a  mere  statement  of  facts.  As  this  method  of  treat- 
ment may  not  l)e  unwelcome  to  a  wider  medical  pu])lic  and.  as 
far  as  I  know,  does  not  exist  in  English  literature.  I  now  pub- 
lish them  practically  in  the  form  of  the  stenographic  report, 
except  for  some  additions  and  explanatory-  notes.  This  accounts 
for  an  unevenness  of  treatment  and  some  local  coloring  in  the 
presented  material. 

I  may,  perhaps,  be  pardoned  if  I  qualify  here  my  stand  in 
teaching  medicine  and  particularly  pathology  in  some  detail. 
The  average  American  medical  student  of  the  present  day  is 
taught  in  his  college  a  large  variety  of  medical  subjects,  but  in  a 


VI  PREFACE 

manner  which,  accordino-  to  nty  experience,  is  not  apt  to  develop 
in  him  a  plastic,  livinii;  and  flexible  conception  in  any  subject,  in 
other  words,  no  independent  thought.  Forced  by  a  rigid,  pre- 
scribed schedule,  which  leaves  him  no  academic  freedom,  in- 
dividual responsibility  and  time  for  thoroughness,  he  memorizes, 
mostly  from  text  books,  lectures  and  recitations,  and  discon- 
nected demonstrations  and  clinics  many  statements  and  some 
facts.  His  conceptions  are  those  of  a  certain  text-book,  of  a 
certain  page,  or,  similarly,  of  notes  of  a  certain  instructor.  They 
are,  if  the  term  is  permissible,  fossilized  and  immovable.  The 
ability  derived  from  personal,  well  directed  experience  under  an 
instructor,  the  ability  to  form  plastic  pictures  of  occurrences 
which  enable  one  to  combine  visual  and  live,  true  ideas  of  patho- 
logical processes  without  becoming  unreliable  and  phantastic, 
are  foreign  to  most  of  our  present  medical  generation.  Thus, 
our  present  methods  of  teaching  resemble  the  dead  inflexible 
formalism  of  the  scholastic  period  taught  in  the  European  uni- 
versities during  the  middle  ages. 

The  medical  graduate  of  to-day  enters  a  hospital,  faces  life 
and  meets  the  keenest  disappointment.  His  hard  and  fast 
text-book  lines  and  schoolboy  classifications,  memorized  care- 
fully for  recitation  and  written  examinations,  are  broken  and 
shattered.  But  worse,  having  no  other  foundation,  no  critical 
judgment  of  relative  values,  which  is  derived  from  historical 
knowledge  of  a  science,  he  is  unable  to  utilize  his  new  experi- 
ence. He  holds  new  parts  of  a  chain,  but  cannot  unite  them, 
much  less  link  them  to  the  old.  It  takes  a  strong  mind,  much 
stronger  than  the  average  medical  graduate  has,  to  evolve 
successfully  out  of  these  complicated  circumstances.  The  others 
are  simply  content  to  again  memorize  actual  experience  in  the 
Hospital,  and  apply  it  as  well  as  they  can.  They  remain  un- 
cultured. 


PREFACE  Vll 

Herein  lies  a  deficiency  of  our  sj'stein  of  instruction.  "  Die 
Welt  des  Sehenden,"  I  hine  heard  Wundt  impressively  sa}'  in 
one  of  his  lectures,  when  I  was  a  student  in  Leipzi<i;,  "  ist  die  der 
GesichtsvorstelIun<ien."  This  view  of  the  <!;reat  ps3'chologist 
is  amply  followed  in  all  European  universities.  Medical  teach- 
ing is  primarily  directed  toward  developing  the  power  of  ob- 
jective observation  and  a  scientific  method  of  thinking.  In- 
struction is  given  not  outside  of  the  hospital,  Ijut  in  the  hos- 
pitals and  in  the  autops}^  rooms  where  things  can  be  seen,  with 
much  personal  freedom  in  work  and  study.  Xothing  is  more 
important  in  the  education  of  a  physician  than  the  development 
of  clear  visual,  anatomical  ideas  of  diseased  processes  and  ability 
to  construct  their  possible  relations.  The  importance  of  this 
''anatomical  idea"  in  the  education  of  the  physician  was  con- 
stantly emphasized  by  Charcot  and  Virchow. 

It  is  to  be  regretted,  therefore,  that  unfortunate  circimi- 
stances  still  make  it  impossible  to  conduct  most  of  our  large 
hospitals  as  academic  institutions. 

But  I  also  view  with  some  fear  for  our  future  in  medical  educa- 
tion the  present  tendency  in  some  of  our  medical  colleges  to 
introduce  specialized  branches  of  pathology,  medicine  and 
surgers'  into  their  undergraduate  courses  at  the  expense  of  the 
morphological  discipline,  instead  of  a  greater  effort  to  properly 
develop  the  opportunities  of  the  latter  in  its  relation  to  clinical 
medicine.  I  would  not  deny  their  value.  Indeed  experimental 
pathology,  medicine  and  surgery  are  very  necessar}^  supplements 
or  better  complements  of  morphology  for  the  elucidation  of 
special  problems  and  in  the  hands  of  experienced  pathological 
anatomists;  they  are  suited  particularly  for  advanced  students. 
But  they  can  never  replace  that  knowledge  which  is  obtained 
from  the  study  of  a  disease.  The  latter  is  an  experiment  of 
nature  which  develops  out  of  ever- varying,  complicated,  external 


Vlll  PREFACE 

and  internal  conditions  which  we  cannot  exactly  artificialh^ 
duplicate  in  causes,  number,  time  and  expressions.* 

Xo  less  a  brilliant  experimental  investigator  and  leader  in 
experimental  pathology  than  Cohnheim  significantly  delivered 
his  own  inaugural  address  in  assuming  the  chair  in  general 
pathology  in  the  University  of  Leipzig,  "  Ueber  die  Aufgaben 
der  pathologischen  Anatomic." 

It  is,  indeed,  a  serious  problem  which  confronts  today,  not 
only  the  general  medical  education  of  our  younger  generation  of 
students,  but  that  of  the  developing  pathologists.  Already  a 
lack  of  thorough  pathologic  anatomical  knowledge,  experience 
and  depth  of  thought  becomes  noticeable  in  much  of  the  recent 
pathological  literatiu-e  on  the  part  of  many  of  those  who  have 
followed  a  one-sidedi  and  more  spectacular  specialization  in 
pathological  research  without  sound  anatomical  foundation. 
Those  who  doubt  my  words  should  read  the  warning  of  Orth  in 
that  matter,  ''  Zur  Bezeichnung  der  bosartigen  epithelialen 
Neubildungen."  Zentralblatt  f.  allg.  Path.  u.  path,  anat.,  11, 
1908,  and  v.  Hansemann  in  Zeitschrift  f.  Krebsforschung,  Vol. 
Vn,  1909. 

A  spirit  of  anatomical  renaissance,  therefore,  permeates 
these  lectures.  But  I  have  also  endeavored  to  emphasize  what 
Cohnheim  in  his  inaugural  address  said  of  pathological  anatomy 
as  contrasted  with  normal  anatomy :  ''  Die  pathologische  Ana- 
tomic ist  gar  nicht  eine  deskriptive  Wisenschaft  in  dem  Sinne 
wie  es  die  normale  ist."  Pathological  anatomy  is  an  explanatory 
discipline.  Its  educational  value  is  therefore  twofold:  It  pre- 
sents the  visual  picture  of  a  process  and  it  discloses  the  genesis 

*  Compare  the  concluding  remarks  of  Marchand  in  the  description  of  the  new 
pathological  institute  at  Loipzip;  in  the  Festschrift  for  the  500th  anniversary  of  the 
University.  In  Austria  a  vci-y  (Ifsirable  separation  of  pathology  into  two  chairs,  patho- 
logical anatomy  and  experinicntal  pathology,  has  already  taken  place;  in  Germany  the 
latter  is  now  taught  by  clinicians.  The  situation  is  very  similar  to  the  state  of  physiology 
and  anatomy  fifty  years  ago. 


PREFACE  IX 

of  the  process,  at  least,  prepares  the  proper  way  for  its  under- 
standin.i!:.  These  points  I  had  constantly  Ijpforo  my  eyes  in 
the  delivery  of  these  lectures. 

Some  may  find,  perhaps,  a  more  extensive  review  of  ele- 
mentary and  <i;eneral  patholo<!,ical  questions  than  may  seem 
warranted  to  tlieni  by  the  nature  of  the  subject  in  a  <iraduate 
course.  After  deliberation,  I  have  concluded,  however,  not  to 
eliminate  them  in  the  publication  of  these  lectures,  for  the  activ- 
ity of  investi<iators  has  been  so  productive  that  such  reviews 
mi<>lit  possibly  be  welcome  to  those  who  have  been  unable  to 
completely  follow  these  subjects.  Some  of  them  have  had 
important  contributions  since  these  lectures  were  ready  for 
publication.  Particularly  in  the  doctrine  of  fat  degeneration 
and  fat  infiltration,  the  views  still  undergo  a  kaleidoscopic 
change. 

Many  of  the  ideas  expressed  in  the  following  pages  are  based 
on  data  collected  by  me  and  former  and  present  assistants  dur- 
ing a  period  of  six  years  at  the  City  Hospital.  My  greatest 
indebtedness  is  to  Dr.  Lindsay  ^lilne,  who  has  sacrificed  much 
of  his  own  time  and  thought,  and  to  whom  I  owe  the  selec- 
tion of  typical  pictures  for  the  accompanying  plates.  They 
were  executed  by  Mr.  Martin,  the  artist  of  the  Russell  Sage  In- 
stitute. The  generosity  of  the  Trustees  of  the  Russell  Sage 
Institute  made  the  publication  possible.  To  the  publishers  I 
owe  very  hearty  cooperation  and  valuable  suggestions. 

I  may  fittingly  introduce  these  lectures  after  the  manner  of 
Morgagni  in  his  great  "  De  sedibus  et  causis  morborum  per 
anatomem  indagatis:"  Crassus  in  Cicero.  '' De  oratore."  II, 
6.  25,  quotes  Lucilius  as  follows :  "  C.  Lucilius,  homo  et  doctus 
et  perurbanus  dicere  solebat  neque  se  ah  indoctissimis  neque  a 
doctissimis  legi  velle,  quod  alteri  nihil  intellegerent,  alteri  plus 
fortasse  quam  ipse.''     '^  C.  Lucilius^  a  learned  and  very  polished 


X  PREFACE 

man  was  in  the  habit  of  saying  that  he  did  not  ivish  to  he  read 

either  hy  the  very  learned  nor  hy  the  very  uneducated;  for  the  latter 

would  not  understand  him,  while  the  former  might  possibly  know 

more  than  he  himself  did.^^ 

HoRST  Oertel. 

Russell  Sage  Institute  of  Pathology,  City  Hospital, 
New  York  City,  November,  1910. 


CONTENTS 


FIRST  LECTUKE  pack 

HisTOKicAL  Introduction  and  Classification 1 

SECOND  LECTURE 

The  Structure  of  the  Normal  Kidney  and  the  Different  Views 
ON  Its  Functions  in  Their  Relation  to  the  Pathological 
Variations 27 

THIRD  LECTURE 
The  Degenerative  and  Exudative  Features  of  Nephritis 45 

FOURTH  LECTURE 

The  Results  and  Terminations  of  Degenerative  and  Exudative 

Nephritis.     Productive  Changes  in  the  Kidney 110 

FIFTH  LECTURE 
Productive  Nephritis.     Changes  in  Other  Viscera.     (Edema 161 

Notes  and  References 201 

Appendix 214 

Classification  of  Nephritis 214 

Non-inflammatory  Lesions  of  the  Kidney,  Occasionally,  but  "Wrongly, 

Grouped  as  Nephritis 214 

Index  of  Names 217 

Index  of  Subjects 221 


THE  ANATOMIC 

HISTOLOGICAL  PROCESSES  OF 

BRIGHTS  DISEASE 


FIRST  LECTURE* 

Historical  Ixtroductiox  axd  Classificatiox 
Gentlemen: 

It  is  with  great  pleasure  that  I  have  followed  your  invitation 
to  speak  to  you  about  the  diseases  of  the  kidney  ordinarily 
grouped  as  Bright 's  disease.  But  I  appreciate,  and  I  think  you 
probably  will  before  I  finish  these  lectures,  the  great  difficulties 
which  present  themselves  in  a  study  of  renal  lesions,  and  more 
particularly  in  that  group  which  we  intend  to  discuss. 

The  diseases  of  the  kidney  differ  in  a  peculiar  way  from  the 
diseases  of  other  organs.   Three  points  enter  into  this. 

First,  there  exists  an  exceptional,  intimate  correlation  of  the 
diseases  of  the  kidney  with  concomitant  or  associated  conditions 
which  we  cannot  dismiss  from  our  consideration  as  we  do  in  the 
study  of  other  organs.  To  illustrate  this  concretely  I  may  say 
that  one  can  investigate  the  inflammations  of  the  lung,  of  the 
heart,  of  the  liver,  or  of  the  spleen,  more  or  less  independently 
of  other  organs.  We  can  abstract  them  from  the  rest  of  the 
body,  so  to  speak,  and  observe  them  independently.  This  is 
hardly  possible,  however,  in  the  diseases  of  the  kidney,  more 
especially  in  Bright's  disease.     I  need  only  to  remind  you  that 

*  Delivered  on  January  14,  1909. 
2  1 


BRIGHT  S    DISEASE 


the  questions  of  hypertroph}^  of  the  heart,  of  oedema,  of  circula- 
ton^  disturbances,  of  changes  in  the  blood-vessels,  of  albumin- 
uria, etc.,  are  so  intimately  connected  with  the  changes  in  the 
kidneys  that  it  becomes  evident  at  once  that  herein  lies  a  con- 
siderably complicating  factor. 

Secondly,  there  exists  great  difficulty,  and  at  the  same  time  a 
much  greater  necessity  here  than  in  almost  any  other  organ,  in 
establishing  a  proper  relationship  between  structural  and  func- 
tional changes.  But  not  only  are  we  almost  entirely  ignorant, 
or  at  least  uncertain,  of  many  of  the  physiological  conditions  of 
the  secretion  and  of  the  part  played  therein  by  the  various  com- 
ponents of  the  kidney,  but  in  the  pathological  variations  we  are 
constantly  confronted  by  obstacles  which  consequently  are  hard 
or  even  impossible  to  overcome. 

Finally,  a  third  factor  which  conflicts,  and  a  rather  personal 
one,  is  the  multitude  of  views  held  with  regard  to  the  normal  and 
pathological  functions  and  the  anatomical  and  histological 
changes  in  the  kidney,  which,  on  account  of  their  number  and 
of  the  peculiar  subjective  tendency  here  displayed,  make  it 
almost  impossible  to  present  them  satisfactorily  and  entirely. 

It  is  by  reason  of  these  conflicting  opinions  that  the  presenta- 
tion of  the  subject  is  difficult,  and  it  will  undoubtedly  plainly 
appear  when  I  review  for  you  in  a  necessarily  short  and  circum- 
scribed way  the  evolution  of  the  various  conceptions  of  the 
character  of  Bright's  disease.  To  a  great  extent  this  is  respon- 
sible for  the  uncertainty  which  exists  even  to-day. 

This  leads  me  to  qualify  the  necessity  of  such  a  historical 
review.  It  is,  no  doubt,  interesting  and  instructive  to  follow 
the  historical  development  of  the  various  views  held  about  any 
disease ;  but  I  consider  it  imperative  in  the  diseases  of  the  kidney, 
because  it  is  impossible  to  have  an  appreciation  of  the  relative 
value  of  the  present  ideas,  unless  we  are  fully  acquainted  with 


IIIS'IV)in('AI.    I.\^IM{()I)l'('TIO\    AM)    fLASSIFICATIOX  3 

the  oriiiiii  of  these  ideas  and  the  developments  throu<;h  which 
they  have  passed. 

It  appears  that  there  are  essentially  three  interwoven,  dis- 
puted points,  and,  as  you  will  see,  fundamental  ones.  The  first 
is,  What  inflammations  of  the  kidney  are  to  be  included  under 
the  lieadiui;-  of  Bright's  disease  ?  The  second,  What  are  the 
characteristic  features  of  this  inflammation?  The  third.  Are 
there  any  non-inflammatory  processes  which  form  essential 
parts  of  this  disease? 

Of  them,  I  consider  the  second  the  most  important.  It  is 
easy  for  you  to  appreciate  that  w^hatever  conception  may  be 
lield  of  an  inflammatorv^  condition  of  the  kidney  is  necessarily 
dependent  upon  the  view  one  has  of  inflammation  in  general; 
and  the  various  views  which  have  been  advanced  from  time  to 
time  center  around  the  evolution  of  this  general  pathological 
conception. 

One  mistake,  too  frequently  made  as  the  result  of  histological 
studies,  is  to  regard  pathological  processes  as  stationary-,  in- 
flexible, of  great  uniformity  in  appearance,  or  at  least  going  on 
with  mathematical  precision  in  temporary'  arrangement.  One 
ought  to  appreciate  from  the  start  that,  as  the  name  implies, 
pathological  processes  are  processes;  that  is,  forever  changing. 
Histologically  we  observe  stages  of  a  process,  but  we  cannot  inter- 
pret them  in  the  sense  of  a  simple  introduction  of  certain  abnor- 
malities into  an  organ,  where  they  lie  more  or  less  like  foreign 
bodies.  Xecessarity,  they  continually  vary,  constantly  influ- 
enced by  conditions  which  again  depend  upon  a  large  number 
of  outside  factors  and  an  equalty  large  numl^er  of  ever-changing 
individual  reactions  on  the  part  of  the  organism.  Strictly 
speaking,  one  might  say  that  there  are  as  many  diseases  as  there 
are  diseased  individuals.  "\Miile  this  is  to  be  taken  into  con- 
sideration in  the  study  of  any  disease,  it  can  much  less  be  dis- 


4  BRIGHT  S    DISEASE 

regarded  in  nephritis.  Diseases  must  be  grouped,  therefore,  with 
a  thorough  appreciation  of  these  possible  variations,  and  the 
stricter  and  more  circumscribed  a  classification,  the  more  faulty 
it  will  always  be.  For  a  definition,  to  be  exact  and  exhaustive, 
must  consist  in  a  repetition  of  all  component  parts  of  a  sub- 
stance or  a  process.  These  it  sets  out  to  systematize.  Thus, 
as  Taine  has  put  it,  '^un  systeme  est  une  explication  de  Tensem- 
ble  et  indique  une  oeuvre  faite."  Diseases  live,  however,  con- 
stantl}"  change,  and  develop.  Influenced  by  innumerable  outside 
and  inside  conditions,  they  defy  strict  codification  in  much  the 
same  manner  that  any  form  of  life  does. 

Guided  by  such  considerations,  I  shall  not  follow  the  plan 
frequently  employed  by  lecturers  in  a  too  dogmatic  and  complete 
presentation  of  the  subject.  It  will  be  my  endeavor  to  present 
essentially  the  certain  anatomical  and  histological  knowledge 
which  has  gradually  accumulated  in  the  course  of  tinie, .  and 
which  constitutes  the  fundament  of  the  whole  structure.  I  shall 
treat  these  changes  in  their  general  genesis  and  relation  to  each 
other  and  to  the  associated  functional  disturbances.  Thus,  al- 
though incomplete,  it  may  serve  you  better  for  future  thought 
and  experience  than  a  recital  of  many  unconnected  facts  and 
ideas. 

Diseases  of  the  kidne}^  have  been  known  for  a  very  long  time ; 
even  the  Bible  mentions  as  important  'Ho  test  a  man's  heart  and 
kidneys,"  which  ma}^  indicate  a  possible  knowledge  of  the  rela- 
tionship between  heart  and  kidneys;  but  reliable  data  do  not 
appear  until  more  thorough  knowledge,  gained  by  autopsies  of 
human  beings,  drew  attention  to  certain  anatomical  changes 
which  the  kidney  may  undergo.  ^Etius,  between  300-400  A.D., 
came  to  the  conclusion  that  certain  cases  of  oedema  and  ana- 
sarca were  associated  with  hardened  kidneys.  This  knowledge 
was  extended  on  the  clinical  side  by  an  equally  good  observer, 


IIISTOKICAI.    IX'lMJOnrCTIOX     AM)    ("I.ASSIFIC  ATIOX  O 

A\i('(Min;i,  ahoul  lOOO.  who  found  thai  in  a  certain  number  of 
these  cases  tlic  urine  was  thin,  watery  and  increased  in  quan- 
tity.' But  it  was  more  ospocially  Mor<i;a,<;iii,"  (Uuin<>;  the  latter 
half  of  the  eiuhteenth  c(Mitui'y.  whom  we  properh' re<i;ard  as  the 
founder  of  pathological  anatomy,  who  described  with  ^Teat  care, 
clinically  and  anatomically,  cases  of  <2;ranular,  contracted  kid- 
neys, associated  with  dropsy.  In  certain  other  observations 
which  he  made  in  order  to  determine  the  cause  of  dropsies  he 
found  healthy  kidneys  but  distinctly  diseased  livers.  Dropsies, 
Avhich  were  then  rei>;arded  as  morbid  entities,  were  therefore  clas- 
sified as  with  and  without  kidney  disease.  A  great  step  toward 
better  knowledge  of  the  diseases  of  the  kidney  was  made  by  Co- 
tiigno  in  1770,^^  who  demonstrated  for  the  first  time  the  occur- 
rence of  serum-albumin  in  the  urine  of  dropsical  patients.  He 
brought  that  fact  into  proper  relation  with  cases  of  oedema  and 
anasarca,  but  erroneously  held  that  it  represented  an  effort  on 
the  part  of  the  organism  to  get  rid  of  the  oedematous  fluid. 

Cruikshank^  elaborated  Cotugno's  findings,  and  found  that 
certain  cases  of  oedema  showed  no  albumin  in  the  urine;  finalh' 
Wells''  demonstrated  the  presence  of  blood  and  albumin  in  the 
urine  of  scarlet  fever.  Gradually,  then,  positive  anatomical  and 
clinical  evidence  accumulated,  which  pointed  more  or  less  closely 
to  the  connection  of  dropsy,  albumin  in  the  urine,  and  kidne}'  dis- 
ease. Early  in  the  last  century  the  examination  of  urine  had 
been  well  elaborated,  particularly  by  Brande  and  Scudamore,** 
who  already  knew  that  albuminous  urine  contained  less  urea 
than  did  normal  urine. 

Bright's  work  w^as  ushered  in  b}'  that  preliminary  knowledge. 
Like  his  predecessors,  he  commenced  his  observations  with  an 
investigation  into  the  causes  of  dropsy,  and  it  was  his  purpose  to 
determine  the  underlying  anatomical  condition.  He  collected 
and  grouped,  very  excellently  indeed,  a  certain  number  of  cases 


6  bright's  disease 

of  oedema  associated  with  changes  in  the  kidney,  and  in  a  similar 
fashion  certain  cases  of  ascites,  anasarca,  or  oedema  with 
diseases  of  the  hver,  and  it  is  mainly  Bright's  credit  to  have 
pointed  out  more  clearly  than  any  one  l^efore  him  that  certain 
cases  of  drops}^  are  constantly  associated  with  certain  changes 
in  the  kidneys,  and  others  equally  with  certain  diseases  of  the 
liver.  These  first  observations  appeared  in  1827 — a  classical 
publication  illustrating  the  great  value  of  thorough,  painstaking, 
objective  observations  and  deductions  therefrom."  It  may  be 
said  that  almost  everything  which  Bright  advanced,  as  far  as 
pure  observation  goes,  has  stood  the  test  of  time  until  to-day. 
The  clinical  pictures  which  he  presented,  particularly  later,  in 
the  first  volume  of  the  Guy's  Hospital  report  on  chronic  renal 
disease,  have  never  been  better  drawn  by  any  later  author,  and 
to-da}^  we  have  no  better  description  than  that  he  gave  us.^ 
Even  on  the  anatomical  side  his  observations  stand  to  a  great 
extent  to-day.  He  properly  correlated  the  hypertrophy  of  the 
left  ventricle  of  the  heart  with  some  diseases  of  the  kidney,  and 
he  advanced  the  same  views  with  regard  to  this  relation  which  are 
held  to-day.  (Particular  attention  ought  to  be  paid  to  the  exe- 
cution of  the  plates  accompanying  his  first  report  of  medical 
cases  in  1827,  and  printed  in  London,  showing  the  excellent 
workmanship  of  that  time.) 

Bright  did  not,  of  course,  finish  his  work  with  this  original 
account,  but  subsequently,  in  the  Guy's  Hospital  Reports,  he 
published  a  number  of  very  important  observations,  extending 
his  original  views  on  the  subject.  He  divided  the  disease  into 
three  groups : 

''  In  the  first  the  kidney  is  apparently  in  a  stage  of  degenera- 
tion, causing  this  organ  to  be  less  firm,  yellow,  mottled.  This 
may  lead  to  an  alteration  characterized  by  a  tuberous  appearance 
of  the  surface. 


HISTORICAL    IXTKODLCTIOX    AND    CLASSIFICATION  / 

"  In  the  second,  the  kidney  is  transformed  into  a  ti;ranulated 
texture,  as  if  fine  (grains  of  sand  had  been  sprinkled  over  it,  and 
sometimes  innumera])le  specks,  of  no  definite  form,  are  equalty 
strewn  over  the  surface.  Later,  the  kidney  assumes  a  tul^erous 
appearance,  as  in  stage  one. 

''  In  the  third,  the  kidney  is  quite  rou<!;h,  with  numerous  pin- 
point projections,  yellow  red  and  purplish.  It  is  hard,  lobulated, 
almost  cartilaginous,  and  contracted." 

In  these  lesions  just  quoted  we  can  recognize  those  which 
are  termed  to-day  acute  nephritis,  chronic  parenchymatous 
nephritis,  and  contracted  kidney. 

I  must  now  touch  upon  an  important  point,  which  you  must 
well  remember,  as  it  is  one  which  subsequently  has  caused  a 
great  deal  of  discussion.  Bright,  from  the  start,  held  that  all 
these  three  stages  were  of  uniform  character,  in  the  sense  that  one 
advanced  to  the  other;  that  all,  then,  stood  in  temporary-  rela- 
tion to  each  other.  He  regarded  the  changes  "'  as  due  to  altera- 
tions in  the  circulations  of  the  kidney,  brought  about  by  in- 
fluences of  the  skin  and  stomach,  or  producing  a  decidedly  in- 
flammatory condition  of  the  kidney.''^  Bright  did  not  think  that 
the  lesions  here  presented  were  the  only  ones  which  were  found 
in  the  kidney,  for  he  described  in  his  original  article  several 
others,  which,  however,  were  regarded  as  of  minor  importance. 

The  ideas  of  Bright  necessarily  attracted  attention,  primarily 
in  England,  and  were  taken  up  particularly  l^y  Christison, 
Osborne  and  Gregory.^  Christison  separated  the  disease  into 
acute  and  chronic  forms,  although  he  held  that  it  was  essentially 
chronic.  He  doul)ted  that  all  the  various  lesions  were  stages  of 
one  morbid  process,  but  left  the  exact  nature  of  it  undetermined. 
He  described  the  following  seven  different  changes  in  the  kidneys : 

*I  partic-ulurly  quote  this  statement  of  Bright's,  as  Lej'den  states  that  the  idea  of 
inflaniination  liad  not  been  expressed  by  Bright,  but  introduced  by  Reinhardt  and  Fre- 
richs.     An  evident  mistake! 


8  bright's  disease 

1.  A  congestion  of  the  kidneys  with  or  without  granular 
deposits  in  the  substance. 

2.  True  granular  degeneration  of  cortical  or  tubular  struc- 
ture,    [a)  Finely  granular,  (5)  botryoidal. 

3.  Degeneration  by  a  smooth,  homogeneous,  yellowish-gray 
mass,  intermediate  in  consistence  between  that  of  the  liver  and 
the  brain. 

4.  Disseminated  tubercles. 

5.  Induration  of  semi-cartilaginous  hardness. 

6.  Atrophy  with  disappearance  of  proper  renal  structure  and 
with  or  without  one  of  the  previous  morbid  states. 

7.  Simple  anaemia. 

He  recognized  these  in  the  following  stages:  Incipient  stage 
of  congestion,  or  reaction.  ^liddle  stage  with  a  nearly  destroyed 
cortex.  Advanced  stage,  where  the  tubular  masses  were  de- 
stroyed. 

Christison  knew  that  the  disease  tends  to  suppress  the  solids 
in  the  urine,  that  it  is  frequently  associated  with  serous  inflam- 
mations and  severe  anaemia,  and  emphasized  the  impregnation 
of  the  bod}^ -fluids  with  urea. 

On  the  other  hand,  some  opposition  arose  on  the  part  of 
Graves,  Elliotson/°  and  Copland. ^^  Graves,^^  particularly,  re- 
garded the  kidney  lesions,  not  as  the  cause  of  oedema,  but  as  the 
result,  believing  that  the  changes  in  the  kidney  were  secondary 
to  an  effort  to  remove  the  oedematous  fluid  from  the  bod}^ 

Further  observations  were  made  by  Willis,  ^'^  who  was  the 
first  to  draw  attention  to  the  fact  that  albuminous  urine  oc- 
curred in  a  number  of  other  conditions  than  had  been  previously 
recognized. 

From  England  the  knowledge  of  this  group  of  diseases  spread 
to  France,  and  was  particularly  taken  up  by  Rayer^^  and  his 
pupils,  Tissot,^'^  Sabatier,^^  Desir,^"  and  Genest.^*^     Rayer  pub- 


IIISroinCAl.    IX'I'IJODICTIOX    AM)    (  IvASSl  I'lCATlON  9 

lishod  an  cxlcnsix'c  valiiahic  nioiio^raj)!!,  j)i'(>s('n1  iiiii'  a  rich  ma- 
terial of  good  observations,  concliiclinf;-  that  Bri<;ht's  disease  was 
an  inflanunatorv  condition  of  tlio  kidney,  essentially  charac- 
terized hy  an  albuminous  ui'ine,  containini;'  less  salts  and  urea 
than  the  normal  and  always  associated  with  a'dema.  He  sharpty 
differentiated  it  from  other  forms  of  inflammation  which  he 
grouped  as  rheumatic  nephritis. 

An  entirely  different  start  in  this  study  was  made  by  Solon.''' 
He  collected  all  cases  of  ''  albuminuria/'  a  term  introduced  by 
him,  and  tried  to  arrive  at  some  conclusion  from  the  material 
thus  collected.  But  inasmuch  as  he  necessarily  included  in  this 
group  cases  of  all  sorts,  some  of  which  could  not  have  even  been 
kidney  diseases,  he  did  not  arrive  at  any  definite,  valuable  con- 
clusion. His  controversy  with  Rayer  did  not  clear  the  matter 
any.  Solon  made  the  observation,  however,  that  the  symp- 
toms of  granular  kidney  frequently  differ  from  the  others,  par- 
ticularly in  an  absence  of  oedema,  but  were  associated  with  nau- 
sea, vomiting,  and  pain. 

The  earliest  histological  investigations  into  Bright 's  disease 
were  made  in  Germany  by  Gluge,  Valentin,  and  Hecht,  after 
BecquereP"  in  France  had  explained  Bright 's  disease  as  a  M^per- 
trophy  of  Malpighian  corpuscles,  which  he  regarded  as  the  secret- 
ing structures  of  the  kidne3^  But  because  of  a  very  insufficient 
and  somewhat  hypothetical  conception  of  the  finer  structures 
of  the  kidney,  they  proved  of  little  consequence.  Gluge-' 
regarded  it  as  inflammation,  as  he  discovered  his  ''characteristic 
inflammatory  globules,"  and  Valentin-^  as  a  disease  of  the  blood, 
being  unable  to  find  any  characteristic  changes  in  the  kidney, 
and  Hecht, "'^  finally,  as  a  degeneration,  analogous  to  his  opinion 
of  cirrhosis  of  the  liver.  Gluge  described  later  three  forms  of  the 
disease.  First,  one  of  inflammation;  second,  a  cirrhosis,  which 
he  meant  in  a  literal  sense,  as  deposits  of  fat;  third,  an  '^uncer- 


10  bright's  disease 

tain"  degeneration.     As  you   see,  an  unsatisfacton^,   deficient 
classification! 

The  great  anatomist  Henle-^  was  the  first  to  give  a  compre- 
hensive, reUable  description  of  the  histology,  and  a  great  many 
of  his  histological  and  anatomical  descriptions  are  considered 
correct,  even  at  the  present  daj^  He  regarded  the  whole  process 
as  an  exudation  of  fibrin  l^etween,  and  into,  the  tubules,  which 
organizes,  contracts,  and  produces  a  cirrhosis  of  the  kidney.  He 
employed  the  term  cirrhosis  in  the  modern  sense  of  connective- 
tissue  formation  with  contraction.  Based  on  his  own  observa- 
tions and  those  of  others,  he  differentiated  between  these  types : 

1.  Steatosis  of  the  kidney  (Gluge  and  Johnson). 

2.  Subacute  inflammation  with  cyst  formation. 

3.  Cirrhosis  of  the  kidney. 

4.  Swelling  of  the  kidney  due  to  oedematous  infiltration  and 
first  stage  of  cirrhosis. 

5.  Acute  desquamative  nephritis  following  exanthemata 
(Johnson). 

The  glomeruli,  in  his  opinion,  were  not  changed.  He  should 
be  particularly  remembered  as  being  the  first  to  give  a  careful 
description  of  tube  casts,  later  studied  thoroughly  by  Xasse, 
Simon,  Scherer,  and  Rovida.  He  held  that  they  were  composed 
of  fibrinous  exudate,  and  similar  views  were  entertained  by  Vogel. 

On  the  other  hand,  Canstatt,-'^  who  with  Siebold  had  studied 
two  cases  of  the  disease,  regarded  the  lesions  as  either  a  non- 
inflammator}^  deposit  of  albuminous  fibrinous  granules,  or  of  fat 
in  the  cortex:  a  ' 'steatosis  renum." 

In  England  there  appeared  about  this  time  Bowman's  great 
work  on  the  finer  structures  of  the  kidney,  which  gave  a  new 
impetus  to  the  study  of  Bright's  disease.  Of  these  works, 
those  of  Johnson,-®  Toynbee,-'  Simon,-^  and  Busk"^  are  of  es- 
pecial importance.      In  these  investigations  there  appears  for 


IIISTOHICAL    I.\TH()I)rrTK)\    ANT)    ("LASSTFH'ATION  11 

the  first  time  an  cik lea xor  to  hold  different  processes  responsil)le 
for  llie  syrni)t()m-c()inplex  and  characteristic  features  of  Bri<!;ht's 
disease. 

Toynhee  was  the  first  to  describe  the  thickenin<i  of  the  arter- 
ies, and  interstitial  cellular  proliferation,  while  Johnson  paid 
particular  attention  to  the  fatty  infiltration  of  the  tubular 
epithelium,  leading  to  what  he  called  a  chronic  desquamative 
nephritis.  He  held  that  this  may  develop  independently  without 
previous  acute  changes,  and  therefore  was  one  of  the  first  to 
discard  the  uniform  view  of  Bright's  disease.  He  recog- 
nized, further,  amyloid  and  fatty  kidney.  Busk's  idea  was  that 
the  contracted  kidney  resulted  from  a  capillar}-  phlebitis,  as 
granular  liver  results  from  a  portal  thrombo-phlebitis. 

Important  contributions  appeared  in  works  of  Reinhardt^° 
and  Frerichs."^^  Reinhardt  regarded  the  lesion  as  a  diffuse 
inflammation  with  a  peculiar  lack  of  organization  on  the  part  of 
the  fibrin,  and  leading  to  a  destruction  of  the  epithelium. 
Frerichs,  extending  these  views,  distinguished  between  the  fol- 
lowing absolutely  correlated  stages:  First,  h3^persemia  and 
beginning  exudation;  second,  exudation  and  metamorphosis  of 
the  exudate;  third,  regression  and  atrophy,  in  which  the  exudate 
may.be  partly  transformed  into  connective  tissue.  This  classifi- 
cation came  into  general  use  l:)efore  Virchow.  On  the  other 
hand,  Rockitansky,'^-  again  separated  exudative  nephritis  en- 
tirely from  Bright's  disease  and  regarded  as  characteristic  of 
that  lesion  a  degeneration  and  desquamation  of  the  epithelium. 
But  he  allowed  a  possible  combination  of  Bright's  disease  with 
nephritis. 

We  come  now  to  a  ver\^  important  turning-point  in  the  histors^ 
of  Bright's  disease,  as  well  as  in  the  whole  historv  of  pathology. 
In  1852  Virchow'^"  published  a  celebrated  article  in  the  fourth 
volume  of  his  ''  Archives,"  on  ''  Parenchymatous  Inflammation." 


12  bright's  disease 

He  was  the  first  to  use  this  term,  which  since  then  has  become 
common  property.  In  it  he  laid  the  corner-stone  for  all  future 
ideas  about  parenchymatous  inflammation,  although  3^ou  will 
presently  see  that  Virchow's  ideas  of  parenchymatous  inflamma- 
tion are  entirely  different  from  what  was  later  regarded  as  such. 
It  may  therefore  be  necessary  to  detail  some  of  his  views  in  that 
relation. 

Before  the  time  of  Virchow,  the  ideas  of  inflammation  may  be 
gained  from  Vogel's  definition :  '^  Inflammation  =  capillary  hyper- 
semia  +  hj^drops  fibrinosus."  Virchow's  observations  led  him  to 
the  conclusion  that  it  was  erroneous  to  regard  the  exudate  as  the 
essential  features  of  any  inflammation,  but  that  the  constant 
characteristic  of  inflammation  was  parenchymatous  degener- 
ation. This  resulted  from  an  excessive  imbibition  of  exuded 
fluid,  which  he  regarded  as  exaggerated  nutritive  material.  It 
led  him  to  the  idea  that  the  inflammatory  process  was  really  a 
nutritive  disturbance  of  parenchyma  cells,  and  he  applied  this 
view  particularly  to  the  kidnej^s.  As  the  result  of  this  excessive 
nutriment  the  cells  become  large  and  swollen,  and  the  albuminous 
molecular  contents  are  increased.  Thus,  he  assumed,  the  pro- 
toplasm of  the  cell  disintegrates  and  becomes  fatty  and  granular. 
In  some  cases  the  whole  of  the  exudate  is  thus  consumed  by  the 
epithelial  cell,  so  that  the  fibrin  does  not  appear,  and  the  only 
evidence  of  the  presence  of  the  exudate  is  found  in  the  albumin 
which  is  carried  off  in  the  urine.  Virchow,  then,  regarded  the 
parenchymatous  change  as  the  essential  feature  of  every  in- 
flammation, and  this  disturbance  of  nutrition,  as  he  termed  it, 
differs  from  simple  degeneration  only  in  degree.  He  concludes 
with  these  words :  "  I  vindicate  above  all  the  degenerative 
character  of  inflammation,  and  although  I  regard  it  as  increased 
nutritive  phenomenon,  I  do  not  see  in  it  an  evidence  of  increased 
strength,  but  an  expression  of  its  diminution." 


HlSTOIilCAl,    I.\TH()I)r("TI()\    AM)    CLASSIFITATIOX  13 

Cliii(l(Hl  l)y  these  considerations,  he  (listin«;uished  l^etvveen 
three  forms  of  nei)hritis,  for  which  lie  created  tlie  followinjj; 
terms,  wliich  ai-e  still  employed  to-day,  althou<;h,  as  you  will 
appreciate,  in  a  dilferent  sense  from  the  one  Virchow  ^ave 
them. 

First,  catarrhal  inflammation,  where  cells  become  granular, 
opaque,  and  break  off  the  basement  membrane. 

Second,  croupous  inflammation.  Here  the  cells  show  essen- 
tially the  same  changes,  l)ut  l)ecome  mixed  with  a  coagulated 
fibrinous  exudate. 

Third,  true  parenchymatous  inflammation,  which  is  the  most 
intense,  and  consists  of  a  granular  swelling  and  disintegration 
of  cells  with  the  formation  of  a  soft  detritus. 

Niemann,  one  of  Virchow's  pupils,  in  his  inaugural  disserta- 
tion (1848),  gives  the  following  interesting  and  excellent  descrip- 
tion of  the  finer  parenchymatous  changes  in  nephritis  in  Vir- 
chow's sense :  "  Qui  quiden  processus  (Infl.  parenchymatosa)  in 
renibus  procedit,  et  quiden  maxime  in  epithelii  cellulis  canali- 
culorum  uriniferorum  contortorum  in  substantia  corticali. 
Epithelii  cellulse  majores  fiunt,  endosmosis  auda,"^  eoriunque  con- 
tentum  mobilum  turbidumque  fit.  Cellulis  autem  amplificatis 
canaliculi  uriniferi  extenduntur  et  renum  ambitus  major  existit. 
Canaliculorum  amplificatione  circuitus  sanguinis  in  vasis  capil- 
laribus  impeditur,  unde  anaemia  renum  oritur,  in  renum  super- 
ficie  astra  venosa  conspiciuntur,  quia  sanguis  venosus  refluere 
nequii. — Turn  cellulse  illse  metamorphosin  adiposam  subeunt, 
emolliuntur,  denique  massam  formant  pultiformem,  quae  urin^e 
admisceri  potest,  quo  urina  fit  adiposa.  Quae  quidem  admixto 
raro  fit,  plerumque  massa  ilia  resorbetur.  Processu  progrediente 
canaliculi  lu-iniferi  collabuntur,  quse  in  renum  superficia  loca 
depressiora    formantur   et   renes   speciem   granulosam   prae   se 

*  Italics  mine. 


14  bright's  disease 

feriint.  Loca  elata  in  renum  superficia  colore  intense  flavo 
portes  sunt,  qiise  metamorphosin  adiposam  non  subierant." 

He,  therefore,  classifies  the  lesion  in  the  three  previously 
detailed  stages.*  It  is  interesting  to  recall  here  that  Virchow 
sharply  differentiated  the  cicatricial  formation  as  the  result  and 
not  as  part  of  the  inflammatory  process.  We  will  learn  that 
such  a  stand  has  only  recently  been  taken  again  by  Aschoff. 

In  1859  Arnold  Beer,  a  pupil  of  Virchow,  stimulated  by 
Bowman's  and  Goodsir's  work,  published  a  monograph  on  the 
connective  tissue  of  the  human  kidney  in  health  and  disease. ^^ 
In  this  he  paid  particular  attention  to  the  interstitial  hyperpla- 
sias in  various  forms  of  nephritis,  which  he  carefully  described, 
alone  and  in  connection  with  the  accompanying  vascular  and 
parenchymatous  changes.  It  is  interesting  to  note,  in  view  of 
Weigert's  later  work  and  ideas,  that  he  inclines  to  the  belief  that 
atroph}'  of  tubules  and  glomeruli  precedes  the  connective-tissue 
hyperplasia,  and  that  the  process  is  more  or  less  of  a  peculiar 
complementary  character.  (Pp.  119  and  122.)  Interesting  is, 
further,  that  he,  as  the  first,  attaches  considerable  significance 
to  the  proliferation  of  the  epithelium  in  nephritis  (p.  125),  which 
explains,  in  his  opinion,  that  kidneys  may  show  microscopically 
small  atrophic  glomeruli  and  appear  granular,  but,  at  the  same 
time,  as  a  whole,  are  of  normal  size  or  even  enlarged.  The 
tubules  in  these  cases  appear  dilated  and  filled  with  hyper- 
plastic epithelium.  Future  investigations  have  unfortunately 
disregarded  this  important  process  of  the  lesion. 

Beer  was,  therefore,  the  first  to  draw  the  interstitial  connec- 
tive-tissue changes  prominently  into  the  discussion.  When  it  is 
further  considered  that  shortly  afterward  appeared  Cohnheim's  ^'' 
classic  observations  on  inflammation,  which  again  placed  the  es- 
sential features  of  that  process  in  and  around  the  vascular  system, 

*  Cited  after  Virchow. 


llISTOliU'AL    l.\TlU)l)lt  Tl().\     AM)    (  I.ASSI  I'lCATlOX  15 

and  wliicli  exerted  a  j»;reat  influence  on  nil  contemporary  investi- 
gators, it  IxM'omo.s  approf'iablo  how  the  attention  contorod  once 
mon^  Mi-onnd  these  chan,<;es.  I'his  influence  i,s  well  shown  in  the 
works  and  (efforts  of  Trauhe'"  to  differentiate  between  a  cir- 
curnscapular  and  intertubular  nephritis,  and  to  nej;"lect  the 
parenchymatous  involvement.  The  subsequent  establishment 
of  glomerulonephritis  as  a  special  type  by  Klebs/^"  and  w^hich 
was  later  regarded  by  Ril^bert'^*^  as  the  universal  incipient  lesion 
of  all  forms  of  Bright's  disease,  brought  equal  support  to  the 
prominence  of  the  vascular  and  interstitial  changes. 

However,  it  remains  Traube's  great  merit  to  have  conclu- 
sively separated  the  cyanotic  and  amyloid  kidneys,  as  non- 
inflammatory, from  nephritis. 

These  views  of  the  purely  vascular,  interstitial  inflammator}^ 
nature  of  nephritis  did  not  entirely  succeed  in  replacing  Virchow's 
conceptions.  As  in  other  scientific  discussions  where  both  sides 
of  an  argument  contain  truth,  both  were  accepted,  Init  un- 
fortunately as  distinct  and  different  types  of  nephritis,  and  it 
became  prevalent  to  speak  of  parenchymatous  and  interstitial 
nephritis  in  a  contrasting  sense. 

This  created  a  very  grave  and  fundamental  error  from  which 
pathology  is  still  suffering  to-day.  It  was  based  entirely  on  the 
too  narrow  definitions  of  inflammation  of  Virchow  on  the  one 
side,  and  of  Cohnheim  on  the  other. 

It  was  Rosenstein^^  who  first  endeavored  to  establish  a 
reconciliation  between  the  two  extreme  views  of  parenchymatous 
and  interstitial  inflammation,  inasmuch  as  he  regarded  epithelium 
as  well  as  interstitial  tissue  involved.  He,  therefore,  advocated 
the  term  and  idea  of  diffuse  nephritis,  originally  introduced  by 
Reinhardt,  and  further  emphasized  that  one  should  differentiate 
between  degeneration  and  inflammation.  Herein  is  expressed 
an  actual  change  in  the  ideas  of  the  character  of  inflammation,  as 


16  bright's  disease 

essentially  represented  by  the  earlier  writers  and  also  by  Cohn- 
heim  and  Virchow.  Whereas  these  considered  an  inflammation 
only  as  an  exudation,  and  Virchow  essentially  as  a  degeneration, 
Rosenstein  intended  to  combine  both  as,  not  necessarily  depen- 
dent, but  correlated  processes.  The  uncertainty,  however,  on 
all  questions  here  discussed  was  particularly  well  shown  in  the 
discussion  of  Bright's  disease  at  the  first  meeting  of  the  German 
Congress  for  Internal  Medicine  in  1882,  where  Leyden,^°  for  in- 
stance, held  that  all  cases  with  albuminous  urine  and  anasarca 
should  be  grouped  as  Bright's  disease,  while  all  others  were  to 
be  regarded  as  nephritis.  This,  of  course,  included  the  non- 
inflammatory^ amyloid  in  the  category  of  Bright's  disease,  while 
a  contracted  kidney  without  oedema  and  albumin  was  to  be  ex- 
cluded.    A  perfectly  untenable  position! 

In  England,  further  studies  gradually  led  away  from  the 
original  ideas  of  Bright.  After  Christison  and  Johnson  had 
doubted  the  intimate  relationship  of  all  forms  of  nephritis,  voices 
in  that  direction  became  stronger.  Particularly  Samuel  Wilks"^^ 
regarded  the  large  white  kidney  and  small  granular  kidney  as 
independent  affections,  followed  by  Grainger  Stewart,^^  and  in 
1872  Gull  and  Sutton  ^'^  went  so  far  as  to  declare  that  arterial  and 
capillarv'  fibrosis  was  the  cause  of  contracted  kidneys. 

In  Germany,  Bartels^*  was  the  first  to  introduce  the  idea 
of  the  independent  character  of  the  so-called  chronic  interstitial 
nephritis  which  he  attributed  to  a  primary  growth  of  interstitial 
tissue.  He  distinguished  it  from  the  so-called  parenchymatous 
form. 

Senator,^^  however,  again  drew  attention  to  the  point  that 
a  sharp  division  between  these  so-called  chronic  parenchyma- 
tous and  interstitial  forms  was  not  possible,  and  that  one 
ought  to  speak,  as  Reinhardt  and  Rosenstein  had  done,  of  diffuse 
nephritis.     At  the  same  time,  he  admitted  that  there  exists  a 


lUSTUliK'AL    JM'liUJH'CTION    AND    CLASSIFICATION  17 

form  of  nephritis  distincl  from  Die  oidinmy  interstitial  type,  in 
the  artoriosclorotic  kidney. 

The  nuxlern  1urnin<;-point  in  tlie  subject  of  nephritis  may  be 
properly  said  io  commence  with  the  observations  of  Wei<i;ert/*^ 
which,  like  Virchow's,  are  important,  not  only  from  the  stand- 
point of  kichiey  patholoj»;y,  but  in  a  much  more  general  sense. 
Weij!;ert  very  stron<;iy  advocated  a  uniform  view  of  all  kidney 
lesions,  and  claimed  that  a  sharp  line  between  the  various  forms 
could  not  be  drawn,  and  that  the}^  represented  only  quantitative 
differences.  His  most  radical  idea  expressed,  however,  was  that 
the  interstitial  inflammatory  and  productive  chani2;es  are  always 
secondarv^  and  caused  by  a  parenchymatous  destruction  or  loss. 
This  idea,  which  has  become  widely  adopted,  is,  as  you  appreciate, 
the  very  opposite  of  Virchow's  conception.  It  marks  the  time 
when  parenchymatous  inflammation  began  to  be  regarded  in  an 
entirely  different  sense  from  that  of  the  originator.  Parenchy- 
matous degeneration  became  no  more  a  nutritive  disturbance, 
but  the  result  of  an  irritant,  and  the  direct  expression  of  its  in- 
jury. It  is  this  conception  of  parenchymatous  degeneration  which 
rules  to-day. 

While  Weigert  held  this  opposing  view  to  Virchow,  he 
nevertheless  brought  parenchymatous  degeneration  in  a  direct 
pathogenetic  relation  to  the  interstitial  changes,  and,  as  I  shall 
have  occasion  to  mention  immediately,  the  present  generation 
does  not  attach  any  more  pathogenetic  significance  to  these 
terms. 

Weigert  distinguished  between  four  intimatety  correlated 
forms:  Acute  nephritis,  characterized  mainly  Ijy  cellular  exu- 
date; the  subchronic  nephritis,  characterized  by  beginning 
connective-tissue  growth;  the  chronic  nephritis,  characterized 
by  a  beginning  contraction;  and,  lastl}',  the  granular  atrophy, 
characterized  b}"^  a  very  complete  loss  of  parenchj^ma. 


18  bright's  disease 

These  ideas  of  Weigert  were  again  stronoly  opposed,  mainly 
by  Ziegler/'  Xaiiwerck,^*  Bartels/^  and,  to  some  degree,  by 
Senator.-'^ 

Xauwerck,  particularly,  drew  attention  to  the  fact  that  the 
dependence  of  the  interstitial  changes  on  the  parenchymatous 
destruction  can  by  no  means  l^e  always  demonstrated. 

Ziegler  follows  Weigert  in  so  far  as  he  also  takes  a  uniform 
view  of  all  hsematogenous  forms  of  nephritis,  believing  only  in  a 
graded  and  no  essential  difference.  That  it  is  possible  to  differ- 
entiate strictly  between  degenerations  and  inflammations  is 
denied  by  Ziegler.  In  opposition  to  Weigert,  following  Bartels, 
he  describes  a  primary  interstitial  nephritis,  the  result  of  a  pri- 
niar\^  connective-tissue  hyperplasia,  leading  to  induration. 

These  ^dews,  opposing  Weigert 's  conclusions,  found  further 
support  in  certain  observations  on  the  so-called  acute  interstitial 
nephritis,  as  first  described  lDy  Biermer,^^  Ernst  Wagner,^-  Klebs,^^ 
and  lately,  with  particular  care,  by  Councilman.^"^  The  latter  re- 
gards this  lesion  as  a  focal  infiltration  by  plasma  cells,  derived 
from  emigrated  lymphocytes;  but  this  cannot  find  its  explana- 
tion in  a  primar}'  epithelial  degeneration,  which  is  always  diffuse. 
AMien  the  latter,  however,  becomes  intense,  polynuclear  leuko- 
cytes are  attracted,  and  not  plasma  cells.  He  argues,  therefore, 
that  the  interstitial  exudate  is  primarv^  and  accompanied  by,  but 
not  dependent  upon,  epithelial  destruction. 

With  this  battle  of  opposing  ideas  still  pending,  a  further 
complication  arose  in  a  gradual  change  in  the  meaning  of  the 
terms  parenchymatous  and  interstitial  inflammations.  This  is 
perhaps  best  illustrated  in  Orth's  position  on  the  subject. 

Orth'^  recognizes  primarily  a  parenchymatous  and  interstitial 
nephritis,  by  which  he  means,  however,  predominating  changes  in 
parenchymatous  and  interstitial  tissue  respectively.  He  uses 
these  terms,  therefore,  purely  in  a  descriptive  sense,  and  not  in  any 


HISTORICAL    INTRODUCTION    AND    CLASSIFICATION  19 

'pathogenc(/C  inc<iin)i(j.     In  this  idea  the  hirgest  nimiher  of  /uitholo- 
gists  and  clinicians  at  present  co7icur. 

As  a  subdivision  and  intermediary  form  he  regards  ^lo- 
menilonephritis.  He  states :^^  "It  has  been  attempted  from 
various  sources  to  estal:)Ush  a  uniform  view  for  all  the  non- 
purulent nephrites,  inasmuch  as  some  hold  that  the  parenchyma 
cells  are  always  primarily  involved,  others  that  all  commence 
with  a  ij^lomeriilonephritis.  I  cannot  a<;ree  with  one  or  the  other 
opinion ;  in  fact,  with  no  exclusive  view  at  all.  As  far  as  I  can 
see,  a  uniformity  exists  only  in  so  far  as  any  inflammatorv'  irri- 
tant chanjres  vessels  as  well  as  tissues,  but  I  hold  it  justifiable  to 
speak  of  various  forms  of  kidney  inflammation,  because  the  dif- 
ferent constituents  of  the  kidney  are  concerned  in  a  most  unequal 
manner.  Following,  therefore,  the  principle  '  a  potiori  fit 
denominatio,'  I  go  so  far  as  to  acknowledge  a  parenchymatous, 
interstitial,  and  glomerulonephritis.  But  it  must  be  remem- 
bered that  no  sharp  line  of  demarcation  between  them  is  possible, 
and  that  their  combinations  are  frequent  findings."  In  this 
sense  he  describes  a  productive  parenchymatous  and  a  productive 
interstitial  nephritis,  of  acute  and  chronic  variety. 

The  ideas  of  Senator  "^^  have  apparently  been  most  widely 
adopted  by  clinicians.  He  holds  that  the  differences  in  the  forms 
of  nephritis  depend  upon  the  course  and  the  duration  of  the 
disease,  and  they,  in  turn,  upon  the  intensity  of  the  irritant.  The 
stronger  the  latter,  the  more  diffuse  and  extensive  the  involve- 
ment. The  weaker  irritant  finds  expression  only  in  parenchy- 
matous attack  (tubules  and  glomeruli),  while  the  interstitial 
tissue  shows  only  hypersemia.  An  acute  interstitial  nephritis 
without  parenchymatous  change  is  denied  by  Senator. 

He,  therefore,  differentiates  between  an  acute  parenchymatous 
(in  the  sense  of  Orth)  and  diffuse  nephritis.  Strictly  speaking, 
a  chronic  parenchymatous  nephritis  cannot  exist,  inasmuch  as 


20 

after  a  time  the  interstitial  tissue  becomes  always  involved;  but 
Senator  holds  that  term  admissible,  to  signify  that  these  changes 
are  primary  and  most  prominent.  But  he  disagrees,  as  pointed 
out  before,  with  Weigert  as  to  whether  parenchymatous  de- 
generation must  always  precede  the  interstitial  change.  He 
holds,  moreover,  that  chronic  inflammations  of  the  connective 
tissue  are  rapidly  followed  by  degeneration  on  part  of  the  paren- 
chyma, leading  to  induration.  Chronic  forms  of  nephritis 
result  either  from  a  previous  acute  condition  or  may  develop 
independently.  Chronic  nephritis  may  also  result  from  arterial 
changes  in  the  kidney,  leading  to  atrophy  of  glomeruli  and 
tubules.  Finally,  any  of  these  chronic  types  may  at  any  time 
undergo  acute  exacerbations,  producing  new,  very  variable, 
anatomical  and  clinical  pictures. 

At  a  recent  discussion  of  the  German  Pathological  Society, 
Miiller^^  again  has  revived  the  discussion  about  the  impossibility, 
even  clinically,  of  differentiating  between  acute  and  chronic 
nephritis,  and  the  erroneous  conception  implied  in  speaking  of 
parenchymatous  nephritis,  because  the  lesion  is  always  diffuse 
and  the  interstitial  tissue  as  much  involved  in  the  process  as  the 
parenchyma,  even  showing  degenerative  changes  in  the  form  of 
fatty  infiltration  (Lohlein).  Again,  in  the  so-called  interstitial 
forms,  it  would  be  erroneous  to  believe  that  the  parenchyma  was 
not  much  involved  and  disintegrated,  for  glomeruli,  as  well  as 
tubules,  show  severe  changes.  He  further  drew  attention  to 
the  difficulty  of  any  satisfactory  etiological  classification;  and 
grouped  off,  much  as  formerly  was  done,  degenerations  from  true 
inflammation  of  the  kidney,  and  recommends  grouping  them  as 
nephroses,  as  contrasted  with  nephritis. 

Finally,  we  must  regard  the  ideas  of  Lohlein,^^  which,  coming 
from  ]\Iarchand's  Institute,  represent  mainly  the  ideas  taught 
there.     He  also  believes  that  in  manv  cases,  which  involve  almost 


HISTOHICAL    IXTHODrrTIOX    AND    CLASSIFICATION-  21 

exclusively  the  renal  {)arenchyina,  as  in  llic  lesions  jjroduced 
by  cholera,  synanche,  poisoninos,  pregnane}',  etc.,  there  exists 
no  real  inflammation,  but  a  de<;eneration,  which  has  a  <iTeat 
tendency  to  heal,  and  prol)a]jly  almost  always  heals  completeh'. 
The  true  nephritis  is  inflammatory  and  has  its  prototype  in  the 
jilomerulonephritis.  The  parenchymatous  changes  there  de- 
pend mainly  upon  the  glomerular  ones  in  their  intensity  and 
duration.  Acute  interstitial  nephritis  must,  however,  be  con- 
sidered independent.  Chronic  nephritis  with  hydrops  results 
from  all  cases  of  glomerular  nephritis  which  do  not  heal,  or 
may  commence  insidiously  without  acute  manifestation;  in 
realit}"  they  represent  the  results  of  an  acute  nephritis. 

Lastly,  the  secondary'  contracted  kidney  alw^ays  presents 
anatomical  e\ddences  of  a  glomerular  nephritis,  which  ma}'  be 
traced  to  previous  acute  lesions.  It  is  certainly  more  frequent 
than  supposed.  In  some  of  these  cases  the  features  are  so 
characteristic  that,  without  knowledge  of  the  previous  history 
of  the  individual,  the  diagnosis  of  nephritis  can  be  made. 

In  this  connection  Lohlein  emphasizes  a  type  of  case  which, 
having  passed  through  an  attack  of  acute  nephritis  wdth  hydrops, 
enjoys  relative  health  for  some  time,  then  suddenly  dies  with  all 
the  -symptoms  of  nephritis.  Here  is  frequently  found  a  typical 
chronic  glomerulonephritis  with  severe  contraction  of  the  organ. 

This,  gentlemen,  is  an  outline  which,  although  incomplete 
and  neglecting  much  and  the  works  of  many,  seems  to  me  to 
contain  the  salient  disputed  points.     What  may  we  conclude? 

With  regard  to  the  question  as  to  what  to  include  under  the 
general  heading  of  Bright's  disease,  I  think  it  has  gradually 
developed  to  limit  its  application  to  the  non-specific,  hsemato- 
genous,  non-purulent  inflammations  of  the  kidney,  and  we  may 
exclude  from  it,  therefore,  all  non-inflammatoiy  affections,  par- 
ticularly the  chronically  congested  kidney  and  its  after-results. 


22  BRIGHT  S    DISEASE 

further  amyloid  and  fatty  infiltrations,  and,  as  will  appear  later, 
the  senile  atrophy  of  the  kidney.  Specific  inflammatory  lesions 
of  known  etiology  or  morphology  have  also,  l^y  virtue  of  their 
characteristic  etiology  and  morphology,  been  eliminated,  as  well 
as  ascending  inflammations  from  the  bladder. 

I  say  that  this  opinion  is  gradually  getting  the  upper  hand; 
some  seem  to  think  that  parenchymatous  degenerative  lesions 
should  enjoy  an  independent  recognition  among  inflammatory 
changes.  To  these  investigators  the  term  Bright's  disease 
appears  still  indispensable  as  a  more  general  one  than  nephritis. 
I  cannot  agree  to  that,  for,  whatever  theoretical  considerations 
may  form  the  foundation  of  that  idea, — and  I  consider  them  very 
slight  indeed, — practically  we  not  only  gain  nothing  by  this  fine 
line  of  demarcation,  but  it  forms  the  source  of  endless  confusion. 
I  shall  qualify  my  position  in  this  matter  more  fully  later. 

The  term  nephritis  will  therefore  be  used  in  the  following 
discussions  as  sjmonymous  with  and  instead  of  Bright's  disease, 
because  it  has  a  certain  definite  meaning  and  cannot  be  misunder- 
stood. We  cannot  agree  as  easily,  and  will  probably  meet 
much  greater  opposition,  in  defining  our  position  on  the  second 
and  most  important  point;  namely,  What  are  the  characteristic 
features  of  this  inflammation?  and,  subsequently,  how  the 
various  inflammatory  processes  in  the  kidney  may  be  ade- 
quately classified. 

Here  you  must  well  remember  what  we  reviewed  a  short  while 
ago.  The  terms  parenchimatous,  interstitial,  diffuse,  persist  like 
threads,  but  of  ever-changing  colors  throughout  the  historic  de- 
velopment of  inflammation  in  general,  and  nephritis  in  particu- 
lar. I  hold  that  the  sooner  we  l^reak  with  their  use,  the  better 
for  the  progress  of  knowledge,  but  particularly  for  our  under- 
standing of  inflammatory  phenonema  and  that  of  nephritis. 

We  have  seen  how  the  views  of  Virchow.  Beer,  C'ohnheim, 


IIlSTOinCAL    I.M'IiOnrC'IMOX    ,\\I)   classificatio.v  23 

VV(M^(Mi,  ;iii(l  ollicrs,  ;ift('i-  wlioiii  the  words  |);tf('iicliymatou.s  and 
interstitial  infianinuitions  were  einploycd  in  a  strictly  patho- 
^eneticnll^'  contrast ini;'  s(>nse,  ha\'o  not  l)f'on  upheld  hy  future 
inv(^st  i,i;at  ions.  It-  is  undeniable  and  clear  that  certain  inflarrnna- 
tory  ii-i'itants  affect  extensively  and  perhaps  primarily  the 
epithelium  in  defeneration  and  proliferation,  and  that  there 
are  othei-s  which  similarly  involve  the  interstitial  and  vascular 
system  in  exudation  and  production.  Both  are,  however, 
always  combined,  correlated,  and,  at  least  after  a  short  time, 
equally  affected,  so  that  in  any  estaljlished  inflammation — in 
other  words,  in  any  nephritis — a  differentiation  between  par- 
enchymatous and  interstitial  inflammation  becomes  practically 
impossible.  But  with  the  pathogenetic  meaning  of  these  terms 
lost,  their  employment  is  no  more  justifial^le,  for  I  cannot  even 
agree  that  these  terms  may  be  used  in  a  purely  descriptive  sense. 

Aside  from  the  fact  that  it  does  not  seem  wise  to  me  to  con- 
tinue terms  in  an  arbitrary  other  sense,  which  is  bound  to  pro- 
duce return  to  confusion  instead  of  an  advance  to  greater  clear- 
ness, this  nomenclature  has  not  even  exactness  in  its  favor. 

We  have  learned,  you  remember,  that  many  changes  which 
some  have  predominantly  related  to  the  parenchyma,  are 
equally  well  and  severely  represented  in  the  interstitial  tissue 
(fatty  degeneration  and  inflammatory  oedema).  Again,  in  the 
so-called  typically  interstitial  lesions,  glomeruli  and  epithelium 
of  the  tubules  are  extensively  affected  and  destroyed.  Who 
could  state,  therefore,  which  were  more  affected  in  one  case  than 
in  the  other?  Such  an  opinion  can  be  based  only  on  very  su- 
perficial examination  of  diseased  kidneys. 

Equall}^  objectionable,  finally,  are  the  two  terms  acute  and 
chronic,  for  they  not  only  do  not  describe  with  any  degree  of 
precision  the  time  limit  of  a  nephritis,  or  the  rapidity  of  its  forma- 
tion and  its  progress,  but  they  have  lost  in  the  course  of  patho- 


24  bright's  disease 

logical  investigations  any  definite  significance  with  regard  to  a 
particular  process  or  group  of  processes. 

As  Mliller  has  pointed  out,  therefore,  the  terms  acute  and 
chronic  have  even  lost  much  of  their  clinical  meaning.  When 
does  an  acute  nephritis  become  chronic?  Here  is  too  much  room 
for  individual  opinion  and  discussion.  Moreover,  kidneys  are 
found  at  autops}^  after  short  illness,  showing  lesions  of  a  character 
now  grouped  as  typicalty  chronic;  and,  again,  after  long-con- 
tinued illness,  showing  predominating  changes  of  so-called  acute 
character. 

Nothing  at  all  is,  therefore,  gained  for  the  understanding  of 
the  pathological  process  b}^  the  terms  acute,  subacute,  and 
chronic;  thej^  may  even  actually  mislead. 

For  all  these  reasons,  and  to  further  progress  in  our  knowledge 
of  the  inflammatory^  lesions  of  the  kidney,  I  propose  to  discard 
all  these  terms,  which,  on  account  of  the  many  ways  in  which 
they  may  be  intended  to  apply,  have  and  always  will  be  the 
greatest  source  of  confusion  and  a  drawback  to  a  better  under- 
standing of  pathological  conditions. 

1 .  The  term  nephritis,  which  in  itself  means  inflammation  of 
the  kidney,  and  which  therefore  comprises  all  the  processes 
which  are  held  to  be  component  parts  of  an  inflammation,  should 
have  added  to  it,  when  necessary,  descriptive  terms,  not  defining 
particularly  the  location  of  the  inflammation  or  its  pathogenesis, 
but  purely  descriptive  of  the  predominating  pathological  feature 
or  features.  In  this  regard  the  classification  of  Delafield  ®°  was 
a  considerable  forward  step. 

2.  In  certain  forms  of  nephritis,  when  predominating  features 
are  lacking  or  of  minor  importance,  no  such  descriptive  terms  are 
required.  These  I  group  as  nephritis  simplex.  This  type  is 
represented  mainly  b}^  varjdng  combinations  of  parenchymatous 
degenerations  and  inflammator}^  oedema. 


inSTOKirAL    TXTRODIT'TION    AND    CLASSIFICATION  Jo 

3.  When  ccrtiiin  inflammatory  attributes  predominate,  they 
are  addcnl  as  (jualifications  to  the  term  nephritis.  In  this  sense 
I  speak  of  nephritis  de^enerativa,  exudativa,  ha'morrha<i,ica,  and 
prohfera.  It  may  be  one  or  more  that  are  marked  in  this  way. 
To  signify  any  particularly  prominent  location,  one  can  add 
tubularis  or  glomerularis. 

4.  When  in  certain  kidneys  fatty  chan<2;es  occur  which  assume 
great  prominence,  the  lesion  is  spoken  of  as  nephritis  degenera- 
tiva  adiposa. 

5.  When,  in  such  kidneys,  loss  of  parenchyma  occurs  with 
connective-tissue  growth  and  vascular  changes,  the  term  nephri- 
tis degenerativa  et  productiva  is  employed. 

6.  When  the  loss  of  kidney  substance  is  extreme,  with  a  thick, 
fibrous,  connective-tissue  growth,  marked  vascular  changes,  and 
the  degenerative  changes  not  prominent,  we  may  speak  of 
nephritis  productiva.* 

7.  Finally,  there  exists  an  atrophy  of  parenchyma,  either 
alone  or  with  marked  arteriosclerosis  and  patchy  fibrous-tissue 
growth,  typified  in  the  senile  kidney,  and,  as  I  believe,  really  not 
of  an  inflammatory  character.  This  is  termed  atrophia  and 
sclerosis  renum  respectively.  I  include  it  here  for  the  sake  of 
discussion. 

No  doubt  combinations  of  these  forms  and  types,  which  we 
can  recognize  only  in  a  wider  sense,  are  frequent,  and  should  then 
be  named  and  classified  accordingly.  This  point  will  appear 
more  fully  in  a  detailed  discussion  later. 

I  trust  you  have  followed  me  sufficiently  to  appreciate  the 
desirability  of  a  break  with  the  older,  current  classifications,  and 
to  substitute  a  simple  descriptive  terminology.  I  believe  fully 
that  onty  on  the  basis  of  clearer  anatomical  pictures,  which  this 

*  The  term  productive  may  seem  objectionable  to  some,  as  the  formation  of  new  tissue 
concerns  largely  the  supporting  structure,  but  it  is  perhaps  admissible  when  it  is  considered 
that  far-reaching  modification  of  cells  occurs  in  the  essential  parenchj-ma. 


26  bright's  disease 

nomenclature  aims  at,  will  better  knowledge  of  the  diseases  of 
the  kidne}'  be  made  possible,  not  only  for  the  minds  of  the  in- 
vestioators,  who  largety  do  not  understand  each  other  now  and 
battle  with  words,  but  particularly  for  those  diagnosing  and 
treating  them. 


SECOND  LECTURE* 

TmK   STRl'CTiaiE   OF  THE   NORMAL    KlDM^V    AM)  THE   DIFFERENT 

Views  on  its  Functions  in  their  Relation  to  the 
Pathological  Variations 

Gentlemen: 

Before  we  enter  upon  our  su}:)ject,  I  think  it  wise  to  rooall 
to  your  mind  certain  histological  and  physiological  facts  and 
theories.  Unfortunately,  they  are  not  as  complete  as  we  would 
like  to  have;  particularly  on  the  physiological  side  testimony  is 
scant.  The  role  played  in  the  secretion  of  the  urine  b}^  the  vari- 
ous component  parts  of  the  kidney  is  not  definitely  settled ;  and 
if  this  knowledge  is  deficient  on  the  physiological  side,  we  are  in  a 
perfect  chaos  of  conflicting  testimony  on  the  pathological  side, 
into  which  we  can  bring  light  and  reason  only  with  much  diffi- 
culty. We  may  admit  from  the  start  that  there  is  really  not  one 
theory  of  urinary  secretion  which  directly  conforms  with  all  the 
pathological  evidence,  and  allows  us  to  form  clear  conceptions  of 
the  pathological  variations.  The  reason  for  this  will  appear 
later.     Let  us  examine  what  evidence  there  is.^ 

Commencing  with  histological  considerations,  I  believe  I  may 
disregard  in  these  lectures  the  embryology,  and  immediately 
invite  your  attention,  with  the  aid  of  this  diagram,  to  the 
structures  of  the  normal  adult  kidney  (Plate  1).  You  know  that 
it  is  composed  of  two  easily  recognizable  and  separable  parts: 
The  outer,  or  cortex,  and  the  inner,  or  medulla,  which  stands  in 
direct  communication  with  the  pelvis.  Both  of  these  enter, 
however,  upon  the  field  of  the  other,  for,  as  you  see,  the  medulla, 

*  Delivered  on  January  21,  1909. 


28  bright's  disease 

by  characteristic  radiating  lines,  sends  offsprings  into  the  cortex, 
known  as  medullary  rays;  while  masses  of  cortex  separate  parts 
of  the  medulla,  the  pyramids,  by  the  so-called  columns  of  Bertini. 
The  medullary  rays  are  produced  by  a  regular  interchange  of 
vessels  with  the  collecting  and  straight  tubules,  the  ascending 
and  descending  loops  of  Henle.  The  cortex  proper,  on  the  other 
hand,  contains  the  glomeruli  and  the  proximal  and  distal  ends  of 
the  convoluted  tubules.  Referring  to  the  diagram,  you  appre- 
ciate the  long  and  partly  tortuous  course  of  one  of  these  units, 
commencing  with  the  cortical  glomerulus,  and,  after  a  long, 
varied  route,  ending  in  the  pelvis  of  the  kidney.  Particular 
attention  should  be  paid  to  the  different  caliber  of  the  tubules  in 
different  parts,  and  the  very  abrupt  change  from  the  broad, 
convoluted  tubule  to  that  of  the  straight,  narrow  limb  of  Henle, 
with  the  interpolation  of  a  second,  but  much  shorter,  convoluted 
portion,  which  finally  empties  into  the  collecting  tubules. 

I  think  it  proper  to  briefly  describe  the  main  features  of  the 
blood-supply  before  speaking  of  their  finer  structure. 

It  is  very  suggestive.  All  conditions  are  given  whereby  a 
large  amount  of  blood,  under  a  very  high  pressure,  can  be  brought 
to  the  kidney  directly,  without  passing  through  many  diverting 
channels.  The  renal  artery  is  a  rather  short,  thick  branch,  given 
off  directly  from  the  aorta.  It  proceeds  to  the  hilus  of  the 
kidney,  where  it  immediately  divides  into  several  branches  which 
ascend  to  the  point  of  junction  between  the  cortex  and  the 
medulla.  The  first  branch  of  the  renal  artery  is  spoken  of  as  the 
interlobar  artery,  while  its  branches,  which  you  see  represented, 
are  spoken  of  as  the  interlobular  arteries.  They  proceed 
up  through  the  cortex  and  down  through  the  medulla.  In  the 
cortex  they  pass  directly  to  the  glomerulus. 

The  formation  of  a  glomerulus  is  interesting.  It  is  a  lobular 
structure,  composed  of  a  vascular  network,  known  as  capillary 


STRTTTTRE    AXD    FT'XrTTOXS    OF    THE    NORM  A  E    KTDXE^'        29 

tufi,  and  enclosed  in  what  is  termed  Bowman's  capsule.  It  is, 
moreovei",  i)eculiar  and  characteristic  that  the  afferent  vessel  of 
the  glomerulus  is  very  nuich  lar<»;er  than  the  efferent  or  centri- 
fugal vessel.  In  other  words,  the  blood  is  brou<iht  under  high, 
almost  dii-ect,  aortic  pressure  to  the  glomerulus,  but  in  the  glo- 
merulus it  is  under  still  higher  pressure  and  distributed  over  a 
relatively  large  surface.  So  much  is  plain  from  anatomical 
observation. 

Having  left  the  glomerulus,  the  vas  efferens  immediately 
breaks  up  into  a  capillary  network,  and  this  network  follows  the 
convoluted  tubules.  Before  the  blood  reaches  the  convoluted 
tubules  at  all,  it  must  go  through  a  glomerulus,  and  the  blood 
which  goes  to  the  tubules  is  under  a  relatively  lower  pressure, 
compared  with  what  prevails  in  the  glomerulus  and,  as  will 
appear  later,  must  have  a  greater  concentration.  The  veins 
which  correspond  to  these  arteries  are  essentially  the  same, 
with  the  only  exception  that  they  do  not  enter  the  glomer- 
ulus. 

The  lymphatic  vessels  of  the  kidney  are  not  very  well  known. 
It  is  supposed  that  they  accompany  the  vessels.  It  is  doubtful 
if  there  are  any  in  the  glomerulus. 

With  regard  to  nerves,  there  exists  a  complex  derived  from 
the  renal  plexus  and  lesser  splanchnic.  They  accompany  the 
vessels  and  also  extend  to  glomeruli  and,  as  some  suppose,  to 
the  epithelium  of  the  convoluted  tubules.  This  latter  point 
is  uncertain,  and  the  presence  of  secretor\'  nerves  has  never 
been  conclusively  demonstrated.  Nervous  influence  may  be 
explained  on  the  l)asis  of  vasomotor  action. 

We  come  now  to  the  important  consideration  of  the  structures 
of  the  essential  parts  of  the  kidney.  The  glomeruli  and  the 
tubules  are  lined  throughout  by  epithelium,  but  it  is  different 
epithelium  in  different  parts.     In  the  glomerulus,  it  is  made  up 


30  bright's  disease 

of  two  layers.  Epithelium  lines  the  capsule  and  is  reflected  over 
the  tuft,  but  only  so  as  to  partly  cover  this.  It  is  stated  b}^ 
Herring-  that  the  epithelium  of  the  capsule  is  of  a  lower,  more 
endothelial,  syncytial  type,  while  the  reflected  epithelium  of  the 
tuft  is  of  a  o-reater  differentiation,  and  resembles  somewhat  the 
secretory  epithelium.  At  the  point  of  entrance  of  the  first 
convoluted  tubule  the  epithelium  changes  gradually,  so  that 
transition  cannot  l^e  definiteh^  established  at  an}^  particular 
point . 

The  epithelium  of  the  convoluted  tubules  is  high,  well 
differentiated.  The  nucleus  is  situated  near  the  tunica  propria. 
The  protoplasm  is  extremely  granular.  These  granulations  are 
arranged  in  definite  order  of  streaks  or  rods.  Their  extremities 
are  delicately  l^rushed  with  non-motile  cilia. 

The  epithelium  of  the  descending  limb  of  Henle  is  low  and 
flat.  It  is  rather  poorly  defined,  so  that  the  line  of  demarcation 
between  the  different  cells  is  not  clear,  and  it  looks  more  like  a 
S}Ticytial  formation  or  the  epithelium  of  the  capsule  of  the 
glomerulus. 

The  epithelium  of  the  ascending  limb  of  Henle,  as  well  as  of 
the  distal  end  of  the  convoluted  tubules,  is  higher,  and  again  be- 
comes distinct^  granular,  somewhat  resembling  the  epithelium 
found  in  the  proximal  limb  of  the  convoluted  tubules.  This  is 
given  by  some  as  c^dindrical  epithelium,  a  doubtful  statement 
for  the  normal  human  kidney. 

The  epithelium  of  the  collecting  tubules,  finally,  is  high,  clear, 
and  not  granular,  while  the  lumen  of  the  tubule  itself  is  very  large. 
You  can  see,  therefore,  that  there  are  essential  differences  in  the 
make-up  of  these  important  structures.  We  are  unable,  how- 
ever, to  correlate  with  the  same  ease  the  functional  difl"erences. 
We  have  evidence  which  brings  in  a  general  way  the  epithelium 
of    these  various  parts  in  relation  to  certain  functions;   but  no 


STIUCTLKE    AM)    Fl.NCTKJXS    OF    THE    XOU.MAL    KID.XKV        31 

absolute  ])r()()f  exists  as  rej»;ards  their  specialized  duties. 
Possible  ex('0])ti()ns  are  only  the  ••lomerulus  and  the  proximal 
coTn-oluted  tul)ul(\  ;il)out  whoso  duties  we  are  somewhat  jjetter 
int'orincd  than  about  the  rest  of  the  structure. 

So  much,  then,  for  anatomical  considerations.  The  arrant;e- 
ment  diflers  from  that  of  other  t^lands  mainly  in  the  blood- 
supjily  and  in  the  peculiar  course  and  structure  of  the 
secreting-  surface. 

I  must  now  review  the  various  conceptions  which  are  held 
with  regard  to  the  secretion  of  urine. ^  The  old  idea  had  been 
that  the  kidney  was  essentially  a  filter,  that  is,  a  structure 
throu*;h  which  water  and  the  characteristic  urinary  constituents 
were  passed  b}^  a  simple  process  of  filtration.  That  idea  gained 
ground  particularly  after  Bowman's  classical  description  of  the 
glomerulus.  But,  on  account  of  the  length  and  the  essential 
structural  variations  of  the  tubules,  it  soon  appeared  that  a 
specific,  secretory  function  on  their  parts  was  also  probable. 
Thus  Bowman  (1842)  ^  himself  believed  that  the  glomerulus 
filtered  water,  l)ut  that  the  tubes  were  a  secretory  structure,  and 
he  based  his  ideas  entirely  on  the  previously  detailed  anatomical 
considerations. 

Ludwig,  who  in  18-44  published  his  classical  observations,  at 
the  time  of  strongest  conflict  between  vitalists  and  mechanists, 
was  the  first  to  offer  a  purely  physical  theory.''  In  substance, 
this  theor}'  assumes  that  ctU  urinary  constituents  transude 
through  the  glomerulus,  under  the  force  of  its  high  pressure  and 
in  ver\^  dilute  solution.  Passing  through  the  tubules  a  resorp- 
tion of  this  water  to  the  more  concentrated  lymph  occurs;  the 
fluid,  therefore,  assumes  its  urinous  character. 

Ludwig  based  his  ideas  of  filtration  on  the  fact  that  the 
amount  of  urine  depends  mainly  on  the  arterial  pressure  and  on 
the  rapidity  of  flow  in  the  kidneys.     If  the  arterial  pressure  is 


32  bright's  disease 

increased,  and  if  the  rate  of  flow  of  the  blood  through  the  kidney 
is  also  increased,  then,  of  course,  the  amount  of  urine  increases. 
If,  on  the  other  hand,  we  have  a  diminution  of  the  arterial  pres- 
sure in  the  kidney,  and  a  diminution  of  the  rate  of  flow  of  the 
blood  through  the  kidne}^,  then  the  amount  of  urine  decreases. 
This  is  a  perfectly  obvious  fact,  and  is  also  supported  by  patho- 
logical evidences.  We  know  that  in  cases  of  incomplete  com- 
pensation of  the  heart  the  amount  of  urine  diminishes  markedly. 
It  is  also  certain  that  when  the  renal  artery  is  obliterated,  the 
same  holds  true;  and  when  the  arterial  pressure  in  the  kidney 
is  markedly  diminished,  as  in  section  of  the  spinal  cord,  there  is 
a  considerable  diminution  in  the  volume  of  urine.  On  the 
other  hand,  division  of  the  renal  nerves  produces  vasomotor 
paralysis  on  that  side  and  the  urine  is  increased.  Stimulation  of 
the  spinal  cord  and  the  splanchnics  raises  the  blood-pressure, 
and  has,  therefore,  the  same  result. 

Further  corroboration  is  found  in  the  close  relation  of  the 
amount  of  fluid  taken  to  that  excreted,  so  that  the  quantity  of 
urine  depends  largely  upon  the  proportion  of  water  present  in  the 
blood.  If  a  person  drinks  large  amounts,  there  is  an  almost 
immediate  response  on  the  part  of  the  kidneys.  The  effects  of 
certain  drugs,  like  caffein  and  diuretin,  have  also  l^een  looked 
upon  as  favorable  to  this  idea,  inasmuch  as  their  action  is  con- 
sidered to  depend  upon  an  increase  of  blood-current  due  to  a 
vascular  dilatation,  although  this  has  been  disputed. 

Now,  in  order  to  explain  certain  properties  of  urine,  which 
cannot  be  accounted  for  by  the  direct  application  of  simple 
filtration,  Ludwig  resorted  to  another  theoretical  consideration, 
which,  in  his  opinion,  explains  the  complicated  and  perplexing 
structure  of  the  tubules.  He  held  that,  while  a  transudation 
occurs  in  the  glomeruli,  resorption  of  water  occurs  in  the  down- 


STKrCTrUE    A.\I)    FUNCTIOXS    OF    THE    NORMAL    KIDNEY        33 

ward  flow.  This  accounts  for  the  relative  concentration  of  the 
urine,  which  is  much  ,i;roater  than  tliat  of  the  blood.  In  his 
opinion,  therefore,  tlic  tubules  exist  mainly  for  the  process  of 
water  resorption. 

It  must  be  confessed  at  once  that  there  is  no  absolutely 
conclusive  proof  of  water  resorption  by  the  tubules,  'i'he  ex- 
periments of  Ribbert  on  the  increased  flow  of  urine  water  after 
the  resection  of  the  medulla  have  been  contradicted  by  Boyd, 
but  latei-  evidence  alon^-  this  line  has  been  particularly  offered 
and  u})held  by  Cushny  and  Hans  Meyer. ^  However,  there  is  also 
much  against  it. 

For,  inasmuch  as  the  urine  has  a  higher  osmotic  pressure  than 
the  blood,  it  follows  that  a  simple  resorption  seems  to  be  out  of 
question,  but  we  must  assume  for  this  active  work  on  part  of  the 
epithelial  cells  of  the  tubules.  It  has  been  figured  out  by 
Dreser"  that,  in  order  to  effect  this  concentration,  it  would  re- 
quire, under  circumstances,  a  force  six  times  greater  than  that  of 
human  muscle  (8000  gm.  per  square  centimeter).  (He  deprived 
a  cat  of  water  for  three  days,  and  then  drew  off  the  urine,  which 
had  a  freezing-point  of  A  =  4.72°  C.  The  l^lood  at  the  same 
time  had  6,  =  0.66°  C.  Now  von  t'HofT  has  shown,  if  A  is 
the  depression  of  the  freezing-point,  and  T  the  absolute  freezing- 
point  of  the  solvent  (for  HgO  273°  and  w  the  latent  heat  of 
fusion  of  ice  =  79  cal.),  then  the  work  A  can  be  reckoned  from 
this  formula : 

dA  =  ^^  X  dv. 

Thus  for  1  per  cent,  solution  of  cane-sugar  (A  =  0.055) : 

, ,        0.055.79 
'^^  =      273^   ^  ^^^- 

To  reduce  this  result  to  gravitation  units,  we  must  multiply 

4 


34  bright's  disease 

by  424,  and  thus  find  that  to  separate  the  volume  dv  of  pure 

water  as  ice  from  1  per  cent,  cane-sugar  solution,  a  force  is  neces- 

,,   ,,                     ,        ,           ,       ^       ,0.055x79x424 
sar}'  equal  to  the  pressure  or  a  column  or  water  oi ^=^ 

meters    in    height.      A    depression    of  /\   =  — 1°   corresponds, 

79  X  424 
therefore,  to  an  osmotic  pressure  of        ^_^      ;    that   is  to   say, 

to  122.7  meters  of  water.  We  have,  therefore,  to  multiply  A  by 
122.7  in  order  to  obtain  the  osmotic  pressure  in  meters  of  water 
in  Siny  solution. 

In  the  case  of  the  cat  just  mentioned,  these  differences  in  the 
freezing-point  denote  an  osmotic  difference  of  498  meters  water, 
i.  e.,  a  pressure  of  49,800  gm.  per  square  centimeter! 

Dreser  has  endeavored  to  show  the  same  with  regard  to  the 
glomeruli,  to  demonstrate  in  them  also  active  work  on  part  of 
the  lining  epithelial  cells.) 

From  our  standpoint  there  are,  as  Miiller^  has  only  lately 
pointed  out,  some  objections  to  accept  the  pure  filtration  idea 
of  Ludwig.  We  all  know  that  in  chronic  venous  congestion  the 
amount  of  urine  is  much  diminished,  while  the  secretion  of 
nitrogenous  material  is  kept  up  to  nearly  normal  limits,  except 
in  extreme  cases  of  oliguria.  How  can  Ludwig  then  account  for 
this?  One  would  have  to  suppose  an  almost  normal  transuda- 
tion from  the  glomeruli  with  an  increased  resorption  from  the 
tubules.  That  seems  unreasonable  from  physiological  and  tele- 
ological  considerations,  for  an  injured  kidney  would  be  called 
upon  to  do  more  work,  to  the  injur}^  of  the  patient. 

For  similar  reasons,  Mliller  holds  an  explanation  of  the  large 
amount  of  urine  in  diabetes  insipidus  difficult,  and  the  same 
applies  to  the  increase  in  urine  in  certain  forms  of  pure  produc- 
tive (interstitial)  nephritis,  where  evidence  showed  greater 
affection  of  the  glomeruli  and  less  involvement  of  the  epithelium 
of  the  tubules. 


STRUCTIRE    AND    FIXCTIOXS    OF    THK    XOH.MAI.    KIDXKY         35 

I  will  point  out  Inter,  however,  tliat  we  must  be  very  careful 
to  directly  apply  patholo*;"ical  funclions  for  the  proof  or  (Hsjiroof 
of  physiolo«iical  contentions,  as  we  ha\e  frequently  entirely 
different  anatomical  conditions  and  rearran«!;ements  of  the 
parts.  I  Ijelieve  Ludwi«i;'s  theory-  particularly  weak  in  its  lack 
of  co'iiiizance  of  certain  metabolic  functions  on  the  part  of  the 
kidney,  besides  the  elimination  of  urine.  We  know  that  certain 
synthetic  processes  are  actively  carried  on  in  the  kidney.  The 
formation  of  hippuric  acid  from  <2;lycocoll  and  benzoic  acid  is 
perhaps  best  known  and  studied;  yet  there  are  undoubtedly 
others,  like  the  formation  of  the  urinar}'  chromogens,  etc.  There 
can  be  no  cjuestion  that  the  epithelium  of  the  tubules^of  course, 
we  do  not  know  w^hich — must  be  actively  concerned  in  this 
formation,  and  that  these  substances  are,  in  all  probability,  dis- 
charged directly  into  the  tubules.  It  certainly  appears  that,  if 
at  all,  a  resorption  of  water  cannot  be  the  sole  duty  of  the  tubules. 

These  ideas  of  Luchvig  have,  therefore,  been  actively  and  per- 
manently opposed,  primarily  by  Heidenhain  and  his  followers. 
Heidenhain-'  took  the  extreme  other  view,  attributing  the  whole 
process  to  an  active  secretion,  and  denying  any  filtration.  His 
ideas  were  essentially  based  on  three  points:  If  one  ties  the  renal 
vein,  the  intraglomerular  pressure  is  increased.  In  spite  of  that, 
the  urine  is  not  increased,  but  diminished.  If  one  ties  the  renal 
arter\'  and  then  releases  it,  the  flow  of  urine  is  not  immediately 
reestablished,  but  only  after  a  considerable  time.  These 
phenomena,  he  argues,  speak  against  a  simple  transudative 
character  of  urine  water.  But  the  fact  to  which  most  importance 
is  attached  is  the  result  of  experiments  after  the  injection  of 
indigo  carmin.  He  found  that,  if  indigo  carmin  was  injected  into 
the  renal  artery  and  the  animal  was  killed  after  ten  minutes,  the 
indigo  carmin  was  always  precipitated  in  the  epithelium  of  the 
convoluted  tubules.    It  was  never  found  anvwhere  else.     From 


36  bright's  disease 

that  he  conckided  a  specific  selective  activity  on  the  part  of  that 
portion  of  the  renal  epithelium. 

Xow,  all  of  these  three  arguments  of  Heidenhain  have  not 
stood  the  test  of  time  undisputed. ^°  The  results  of  tying  the 
renal  vein  and  thus  increasing  the  intra-glomerular  pressure 
without  increase  of  urine,  may  easily  be  attributed  to  venous 
stasis.  A  diminution  in  the  amount  of  urine  may  there  be  due 
to  purely  mechanical  causes,  namely,  pressure  of  the  parts  against 
another,  a  result  of  the  venous  engorgement. 

Similarly,  the  second  argument,  tying  the  renal  arter}^,  with- 
out, on  its  release,  obtaining  an  immediate  flow  of  urine,  appears 
of  doubtful  value,  because,  in  a  complicated  structure  like  the 
kidney,  it  would  take  considerable  time  before  normal  pressure 
and  rapidity  of  flow  are  reestablished  in  the  glomeruli. 

Finally,  the  most  important  argument  which  he  advanced, 
the  results  obtained  from  injection  of  indigo  carmin,  has  been 
denied  its  value  by  many  investigators  who  claim  that,  if  the 
solution  of  indigo  carmin  is  not  of  the  exact  concentration 
Heidenhain  employed,  and  if  the  kidney  is  examined  early  after 
injection,  this  substance  is  also  found  in  the  glomeruli,  so  that 
in  reality  selective  activity  does  not  occur.  It  has  further  been 
pointed  out  that  on  its  way  a  good  deal  of  the  pigment  might 
undergo  a  reduction,  whereby  it  would  not  be  visible  in  other 
cells,  and,  finally,  much  of  the  indigo  carmin  in  the  epithelial 
cells  of  the  convoluted  tul^ules  is  nearer  the  lumen  of  the  tubule, 
so  that  one  might  argue  that  it  were  on  its  way  from  the  lumen 
to  the  ):)lood,  and  not  vice  versa.  This,  of  course,  would  conform 
with  Ludwig's  views. ^^ 

You  see  that  these  ideas  of  Heidenhain,  although  accepted  by 
many,  stand  on  a  ver}^  disputed  experimental  basis. 

Grave  pathological  evidence  has  also  been  brought  forward 
against  the  sweeping  secretory  ideas  of  Heidenhain  by  Senator.^- 


STHrCTrHK    AM)    FrXCTIOXS    OF    TIIK    XOKMAL    KID.XKY        37 

We  know  ;i  tminhci'  of  kidney  lesions  associated  with  extensive, 
alt  liou.i;li  slowly  |)i'o,iiressin<i;,  desl  ruction  of  the  epithelium. 
Accej)t  ini;-  I  leidenliain's  \'ie\vs  of  a  ])urely  secretory  function  of 
the  epitlieliuni,  one  sliould  reasonably  expect  a  gradual  diminu- 
tion in  tiie  amount  of  urin(^  in  those  lesions.  But  the  facts  speak 
differently. 

Patholo<;ists  and  clinicians  have  known  for  a  lon<;-  time  that 
in  certain  types  of  productive  nephritis,  and  in  the  amyloid 
kidney,  the  amount  of  mine,  instead  of  bein<^'  diminished,  is 
actually  markedly  increased.  The  gradual  loss  of  epithelium  of 
glomeruli  and  tubules  does  not  seem  to  have  the  slightest  relation 
to  the  urine  output.  How,  asks  Senator,  can  this  be  regarded  as 
the  active  product  of  the  epithelium? 

Senator,  in  conjunction  with  Munk,  began,  therefore,  to  in- 
vestigate that  point  further. ''^  They  were  aided  by  a  disco ver}% 
made  shortly  before  by  Roy  and  others,  namely,  that  it  is  possible 
to  have  kidneys  functionate  after  they  have  been  removed  from 
the  body.  Taking  advantage  of  this  method,  they  transfused 
defibrinated  blood  through  kidneys,  and  were  able  to  observe 
closely  the  results  of  changing  pressure  and  rapidity  of  flow 
brought  about  artificially  in  transfusion.  They  found  the  fol- 
lowing facts :  In  active  hypersemia — in  other  words,  when  the 
pressure  as  well  as  the  velocity  of  the  flow  is  increased — the 
quantity  of  urine  excreted  increases.  The  quantity  of  nitrogen 
increases,  while  that  of  the  sodium  chlorid  shows  very  little  va- 
riation from  the  normal.  That  latter  point  is  interesting  and 
important  to  remember. 

Then  they  did  the  opposite,  diminishing  the  quantity  and  the 
pressure  through  the  kidney,  with  these  results,  that  the  amount 
of  urine  decreased  decidedly,  that  the  amount  of  nitrogenous 
material  also  decreased  decidedly,  while  the  amount  of  sodium 
chlorid  showed  no  difference  from  the  normal.     Incidentalh',  I 


38  bright's  disease 

should  mention  that  the  amount  of  albumin  which  such  an 
artificial  urine  always  shows  diminished  with  arterial  hypersemia, 
and  increased  with  passive  hypersemia.  Interesting  is  the  ex- 
cretion of  sodium  chlorid,  which  remained  practically  unaffected 
by  active  hypersemia  or  stasis.  It  argues  for  an  at  least  partly 
transudative  character  of  the  urine,  for  pressure  and  rapidity  of 
a  transuding  fluid  determine  the  quantity  of  a  transudate,  but 
not  its  amount  of  dissolved  crystalline  substances. 

Based  on  these  considerations,  they  concluded  that  the  urine 
must  be  regarded  partly  as  a  transudation  and  partly  as  a 
secretion.  The  transudative  part  is  furnished  by  the  glomeruli, 
the  arrangement  of  which  is  also  very  much  in  favor  of  its  being 
a  transuding  membrane.  This,  however,  has  added  to  it  on  its 
way  through  the  tubules  a  secretion  of  the  epithelium,  which  is 
also  in  watery  solution.  The  combined  fluid  is  taken  up  by  the 
collecting  tubules  and  discharged  into  the  pelvis  of  the  kidney 
as  urine. 

These  ideas  also  have  undergone  revision  by  other  investi- 
gators. It  has  been  urged  that  it  really  has  not  been  demon- 
strated beyond  doubt  that  the  glomeruli  filter  only  water  and 
sodium  chlorid,  and  as  a  contradictory  fact  is  mentioned  that  in 
argyria  the  silver  impregnates  the  loops  of  the  glomerular  tuft. 
It  is,  therefore,  argued  that  these  tufts  are  probably  permeable 
for  other,  normal,  urinary  substances.  Again,  it  has  been 
claimed  that,  if  the  glomeruli  truly  filtered,  sugar  as  well  as  albu- 
min ought  to  be  found  in  normal  urine. '"^ 

All  of  these  objections,  however,  carry  very  little  weight. 
That  a  foreign  substance  like  silver  is  arrested  in  the  glomerular 
tuft,  which,  on  account  of  its  arrangement,  seems  to  he  particu- 
larly exposed  to  the  accumulation  of  foreign  material  within  its 
loops,  cannot,  in  my  opinion,  carry  much  evidence  as  regards 
normal  functions.     The  other  two  objections  have  lost  much 


S'l'KlC'nin-:    AM)     FIXC'IMONS    OK    'I'll  I-]     XOH.MAI.    KIDXin'         '49 

,ii,i'()im(l  since  it  li;is  hccoinc  uciU'i'nlly  known  that  \'ar\'in^  traces 
of  all)uniin  occui'  in  all  ucincs,  ;in(l  that  su^'ar  circulates  in  colloid 
form.  Hans  Meyer  helieNcs.  therefore,  tliat  the  <2;lomeruli  filter 
all  the  substances  which  are  contained  in  the  blood  in  crystalline 
foini,  while  the  convoluted  tubules  secrete  such  substances  as 
are  in  colloid  state  (urea,  uric  acid,  phosphoric  acid).  He  and 
other  investi«2;ators  have  revived  for  this  latter  process  Ludwi<^'s 
idea  of  water  and  XaCl  resorption. 

Hans  Meyer,  Cushny,  and  Hausmann  found,  as  previously 
mentioned,'"'  after  extirpation  of  the  medulla,  an  increase  of  from 
three  to  four  times  in  urine  quantity  with  a  proportionate  de- 
crease in  concentration.  ^leyer  states  that  "  the  excretion  of  CI 
and  X  after  such  operation  corresponded  to  the  contents  of  the 
blood,  so  that  the  fluid  equaled  an  albumin-free  blood  filtrate." 

Hans  ^leyer,  Lowi,'^  Gottlieb,  Magnus,''  and  Cushny  also 
found  that  after  injection  of  sodium  sulphate  ( Glaubersalz ) 
into  the  blood,  a  much  more  active  diuresis  occurred  than  after 
injection  of  a  correspondini;-  amount  of  sodium  chlorid.  Meyer 
concluded,  therefore,  that  this  acted  similarly  in  the  kidney  as 
in  the  i2;ut,  prevented  resorption,  and  caused,  so  to  speak,  a 
renal  diarrhea.  It  has  also  been  shown  l)y  Cushny,  Pfaundler,'^^ 
and  Steyrer  '^  that  resistance  in  the  ureters  is  associated  with  the 
secretion  of  a  very  thin  urine.  But  this  latter  might  easily  be 
attributed,  as  Erich  Meyer -°  remarks,  to  a  kidney  injury  which 
interferes  with  its  secretion. 

Against  the  idea  of  filtration  of  dissolved  crs'stalline  sul)- 
stances  by  glomeruli  and  secretion  of  colloid  compounds  by  the 
tubular  cells,  again  are  Asher  and  his  pupils.-^  who  found  no 
regularity  in  the  excretion  of  urine  water  and  XaCl,  and  conclude, 
therefore,  secretion  of  even  these  substances. 

Asher  furthermore  points  out  that  even  specific  glands,  like 
the  salivary,  show  a  ])roportionate  relation  of  dissolved  l)lood 


40  bright's  disease 

constituents  and  water.  But  it  must  be  remembered  that  no 
other  pure  gland  responds  so  instantly  to  changes  in  the  con- 
centration of  the  blood. 

Finally,  Erich  Meyer, -^  who  has  studied  very  carefully  the 
elimination  of  urine  in  diabetes  insipidus  and  other  polyurias,  is 
of  opinion  that  this  urine  cannot  be  regarded  as  a  filtrate  of 
blood-serum,  inasmuch  as  it  is  too  dilute  as  regards  its  total 
concentration,  but  as  regards  urea,  about  ten  times  as  concen- 
trated. For  instance,  in  a  case  with  a  total  urine  amount  of 
8000  c.c.  and  a  nitrogen  excretion  of  11  gm.  pro  die,  the  percent- 
age of  urea  contents  would  be  about  0.3,  while,  according  to 
Gottlieb,  the  blood  only  has  a  concentration  of  0.03  to  0.05. 
On  the  other  hand,  the  CI  content  of  this  urine  was  on  some 
da^^s  almost  ten  times  less  than  that  of  the  blood.  He  further 
found  that  the  diuretic  theocin,  produced  in  diabetes  insipidus 
an  increase  of  concentration  without  increase  in  quantity,  but 
this  could  not  be  explained  by  a  disturbance  of  resorption. 

Similar  to  the  modernized  conception  of  Ludwig  are  the  ideas 
of  Koranjd,"^  whose  views  I  will  mention  in  detail,  because  they 
acquired  considerable  practical  importance. 

He  believes  that  the  glomeruli  filter  only  water  and  sodium 
chlorid,  but  that  in  the  tubules  occurs  an  equimolecular  exchange 
with  metabolic  products:  a  purely  physical  process.  The  so- 
dium chlorid  of  the  urine  is,  therefore,  inversely  proportional  to 
the  amount  of  nitrogen.  Based  upon  this  fact,  which  is  actually 
found  in  a  number  of  conditions,  he  established  the  so-called 
urinar}^  quotient.  This  is  obtained  by  dividing  the  freezing- 
point  L  of  the  urine  by  the  amount  of  sodium  chlorid,  ^^^j— tti  = 

urinar}'^  quotient.  This  quotient,  in  Koranyi's  opinion,  depends 
upon  the  rapidity  of  flow  of  blood  through  the  kidneys:  With 
diminished  flow  the  quotient  is  high;   vice  versa,  with  increased 


STRUCTURE    AND    FUNCTIONS    OK    THE    NORMAL    KIDNEY        41 

flow  the  (|ii()li('iit  is  low.  'i'liis  lias  \)Oon  found  correct  in  cases 
of  heart  disease^  with  failui'e  of  compensation  and  a^dema. 

It  is  interesting-  to  know  that  in  cases  of  orthostatic  or  physio- 
logical alljiiminuria  the  quotient  has  been  found  high,  very  much 
as  in  circulatory  disturbances,  while  in  true  nephritis  with  allni- 
minuria  it  was  about  normal,  provided  no  change  in  heart 
compensation  occurred.  It  has,  therefore,  been  urged  to  employ 
this  method  for  differentiation  of  orthostatic  and  nephritic 
albuminuria.  Here,  again,  repeated  investigations  have  been 
unable  to  maintain  what  was  originally  claimed.  Miiller,  for 
instance,  states  that  it  fails,  particular^,  in  the  convalescence  of 
pneumonia,  as  well  as  in  diabetes  insipidus,  when  the  percentage 
of  chlorids  and  achloricls  rises  and  falls  synchronously. 

One  fault  of  these  theories,  as  in  the  old  conceptions  of 
Ludwig's,  is  their  disregard  of  the  metabolic  activity  of  the 
kidne}',  besides  elimination  of  preformed  nitrogenous  w^aste- 
products  from  the  blood.  This  must  certainly  be  carried  on  In' 
the  tubular  epithelium,  and  the  products  discharged  by  them 
into  the  tubules.  Moreover,  analysis  of  anatomical  and  phj'si- 
ological  evidence  indicates  that  the  production  of  urine  can  not 
be  regarded  as  one  uniform  process.  This  complexity'  un- 
doubtedly accounts  for  the  many  in  parts  conflicting  observa- 
tions and  opinions. 

In  the  production  of  urine  there  appear  to  be  concerned  two 
processes:  The  first  is  transudation,  and  the  second  secretion. 
The  structure  of  the  glomerulus,  as  well  as  what  we  know  of  its 
function,  supports  the  contention  that  we  have  here  a  process  of 
transudation.  (Recently  Brodie  has  further  emphasized  the 
fact  that  the  glomerulus  acts  a  good  deal  like  a  pump;  l)y  virtue 
of  the  elastic  capsular  fibers  the  filtered  water  may  l^e  put  under 
high  pressure,  in  which  it  is  aided,  of  course,  by  the  abrupt 
narrowing  of  the  tube  below.  Thus  it  flushes  away  the  secretion 
of  the  epithelial  cells.)     That  the  glomerular  epithelium  is  secre- 


42 

tory  seems  improbable,  for  the  reason  that  it  only  partly  covers 
the  iilomerulus,  that  it  has  not  the  morphotic  character  of  secre- 
tory cells,  and  that,  under  pathological  conditions,  water  dis- 
charge continues  after  its  loss,  unless  there  is  a  mechanical 
obstruction  to  its  outflow,  or  the  tuft  becomes  diseased.  This  is 
particularly  well  illustrated  in  cases  of  contracted  kidney,  and 
in  some  cases  of  stasis,  when  the  epithelium  has  been  lost,  but 
the  tuft  itself  remains  and  still  functionates.  It  is  further  corrob- 
orated by  the  fact  that  the  reaction  of  the  glomerular  product 
has  l^een  found  alkaline,  and  that  on  increased  diuresis  the  urine 
becomes  alkaline,  and  lastly  by  the  constant  presence  of  vary- 
ing faint  traces  of  serum  albumin  in  all  urines.  The  glomer- 
ulus, therefore,  is  that  organ  whose  duty  it  is  to  regulate  the 
concentration  of  the  blood. 

Now,  we  must  remember  that  this  water,  which  is  furnished 
by  the  process  of  transudation  from  the  glomerulus,  is  modified 
on  its  way.  That  modification  cannot,  I  believe,  be  explained, 
at  least  at  present,  on  a  physical  basis.  We  must  assume  that 
the  epithelium  of  the  convoluted  tubules,  as  well  as  that  of  the 
other  tubules,  plays  an  active  part  in  the  modification  of  that 
fluid  to  urine.  The  reasons  for  it  are  these:  The  osmotic  pres- 
sure of  the  urine  is  much  higher  than  that  of  the  blood,  and  it 
contains  specific  substances,  and  in  such  varying  amounts,  that 
an  active  part  of  these  epithelial  glandular  cells  is  made  most 
probable.  It  is  undoubtedly  for  this  reason  that  the  blood  is 
furnished  to  the  epithelial  cells  of  the  tubules  in  a  much  more 
concentrated  form.  The  change  from  alkaline  blood  plasma  to 
acid  urine,  however,  can  be  explained  on  physical  basis. 

The  anatomical  arrangement  of  the  tubules  indicates  that 
there  must  be  stagnation  of  the  transuded  water  in  the  con- 
voluted tubules.  This  may  be  for  the  sake  of  water  resorption, 
but  to  me  it  is  rather  more  for  the  purpose  of  complete  solution 
of  nitrogenous  elements  discharged  by  the  epithelium   of  these 


STHl'f  TrUM    AM)    FIXCTIOXS    OF    ^HK    XOiaiAI.    KIDXK^'        43 

tuhiilcs.  'I'liis  is  in  harmony  with  the  observations  made  in  cy- 
anosis of  the  ki(hiey,  whore  the  urine  water  is  diminished,  hiil  ihc 
nit  i(),i;('noiis  conlents  about  normal.  On  account  of  the  venous 
stasis,  less  water  transudes  through  the  <>;lonieruli,  but  tlic  func- 
tions of  the  epithelial  cells  are  carried  on  properly,  until  they 
bej;in  to  suffer  from  nutritive  disturbances.  The  urine  is,  tliere- 
fore,  concentrated.  A  theory  of  exclusive  water  resorption 
would  hardly  accoiuit  for  this  phenomenon. 

It  is  also  possible  that  water  resorption  occurs  only  when  the 
amount  of  transuded  water  exceeds  certain  limits.  We  must 
confess  ignorance  of  the  specialized  functions  of  the  various 
parts,  and  types  of  epithelial  cells,  composin*;-  the  tubules,  and 
of  the  details  of  the  secretory  act. 

A  few  words  about  the  discharge  of  the  urine  from  the  pelvis 
of  the  kidney  into  the  ureter  and  bladder.  The  physiological 
text-books  leave  us  in  the  dark  about  the  mechanism  of  this 
process,  although  we  are  informed  that  the  urine  is  propelled 
by  active  contraction  of  the  ureters  into  the  bladder,  and  that  a 
return  flow  from  the  pelvis  into  the  tubules  is  made  impossible 
by  compression  of  the  tubular  orifices  by  any  increase  in  pelvic 
pressure.  Both  pelvis  of  kidney  and  ureter  have  essentially 
the  same  structure;  they  are  strong,  elastic,  muscular  organs, 
lined  by  mucous  membrane,  and  it  appears  probable  that  the 
active  waves  propelling  the  urine  through  the  ureter  into  the 
bladder  take  their  origin  in  the  pelvis  and  similarly  force  the 
urine  into  the  ureter.  This  has  for  us  considerable  interest. 
In  many  long-continued  diseases,  but  notabty  in  the  senile 
kidney,  there  occurs  marked  weakening  of  the  elastic  muscular 
layer  of  the  pelvis,  with  the  result  that  this  gradually  dilates  to  a 
condition  of  hydronephrosis,  although  no  mechanical  obstruction 
outside  of  the  kidney  exists,  and  the  ureters  and  bladder  are  not 
dilated.  In  these  cases  the  pelvis  evidently  loses  its  power  of 
active  discharge  into  the  lu'eter. 


44  bright's  disease 

I  believe  that  this  covers  as  much  as  we  are  justified  to  assume 
at  present  about  the  secretion  of  urine.  Much  is  still  uncertain 
and  contradictory.  We  confess  its  deficiency  and  uncertainty, 
and  there  exists  great  difficulty  in  the  application  of  the  experi- 
mental physiological  knowledge  for  the  explanation  of  diseased 
functions.  In  this  connection,  I  would  like,  however,  to  empha- 
size certain  points,  which  may,  at  least  to  some  degree,  account 
for  these  discrepancies.  It  appears  that  we  are  unable  to  trans- 
pose directly  physiological  knowledge  for  the  explanation  of 
pathological  phenomena  for  the  following  reasons:  The  patho- 
logical organ  is  essentially  a  different  organ  from  the  normal.  It 
presents  more  than  simple  alterations  of  physiological  processes, 
in  exaggeration,  diminution,  or  abolition  of  certain  functions 
which  depend  on  similar  organic  changes.  It  is  really  in- 
comparable to  the  normal  organ  from  which  it  developed. 
Its  whole  architectural  arrangement  is  changed  by  the  formation 
of  new  tissue  and  the  introduction  of  new  cellular  elements; 
its  channels  of  nutrition,  lymph,  and  nerve  distribution  become 
fundamentally  altered;  secretory  ducts  are  lost;  new  ones  are 
created;  new  cell  types  develop  from  the  preexisting  par- 
enchyma cells;  in  short,  the  pathological  organ  is  a  new  one, 
characterized  by  tissue  of  its  own  and  specific  arrangement  of 
its  parts.  No  wonder,  therefore,  that  it  presents  functional 
phenomena,  which  cannot  be  fully  covered  or  explained  by  a 
direct  application  of  the  results  of  simple  physiological  experi- 
mentation and  consideration  derived  from  the  normal  organ. 

Here  is  a  future  field  for  pathological  anatomy.  It  can  no 
longer  be  satisfied  to  describe  and  disclose  tissue  changes,  but  it 
must  construe  the  plan  of  the  whole  pathological  organ.  Only 
a  knowledge  of  both  will  ultimately  lead  to  an  intelligent  under- 
standing of  pathological  functions  of  a  whole  organ,  and  estab- 
lish a  pathological  physiology  commensurate  with  the  normal. 


THIRD   LKCTUPJ:* 

The  Dkgienerativk  axd  IOxtdative  Featlkes  of 

Nephritis 

(IvnlU)in'n: 

FoUowiiii;'  the  classification  indicated  at  the  end  of  tlie  first 
lecture,  I  turn  to  a  detailed  description  of  nephritis  simplex.  I 
understand  l)y  it  a  diffuse  inflammation  of  the  kidney,  charac- 
terized by  parenchymatous  degeneration  and  inflammatory 
oedema;  that  is,  serous  exudate  with  diminished  resorptive 
ability.  This  type  of  kidney  lesion  is  now  variously  classified  as 
acute  nephritis,  or  acute  parenchymatous  nephritis,  or  acute 
parenchymatous  deoeneration  of  the  kidney.  The  impropriety 
of  the  first  two  terms  I  have  already  covered,  but  I  am  ol^lioed 
to  pay  some  attention  here  to  the  last, — the  acute  parenchyma- 
tous degeneration  of  the  kidney, — inasmuch  as  strong  attempts 
have  been  made,  only  quite  recently  again,  to  separate  the 
degenerative  lesions  of  the  kidney  from  the  inflammations. 
This  has  been  strongly  advocated  by  Miiller,^  who  wants  to 
substitute  the  term  nephroses  for  all  such  non-inflammatory  but 
essential  degenerations,  and  Marchand,  and  Lohlein  and  Heineke,- 
with  some  others,  look  more  or  less  favorably  upon  such  classifi- 
cation. The  evidence  for  it  is  that  there  exist  some  diseases, 
cholera  foremost,  and  some  intoxications,  like  those  of  phos- 
phorus, chromium,  and  corrosive  sublimate,  in  which  extensive 
parenchymatous  degeneration  occurs  primarily  and  prominently, 
which  may  or  may  not  become  associated  later  with  inflamma- 
tory hemorrhages  and  cellular  exudate,  and  finalh^  with  pro- 
ductive interstitial  changes. 

*  Delivered  on  Fcbnuiiy  4,  1909. 
45 


46  bright's  disease 

Marchand,^  speakino;  of  the  kidney  changes  in  corrosive 
subhmate  poisoning,  argues  that  one  is  not  justified  in  regarding 
the  initial  lesion  as  a  nephritis,  inasmuch  as  the  degeneration  is 
the  direct  primars^  effect  of  the  poison,  and  that  death  or  re- 
generation may  occur  without  additional  inflammatory^  reac- 
tions. These  latter,  he  holds,  are  only  the  late  result  of  a 
chemotactic  action  caused  by  the  accumulation  of  necrotic  cell 
material  and  not  reduced  by  the  poison  itself,  which  has  long 
before  ceased  to  exert  its  influence. 

But  Marchand  himself  admits — and  this  is  very  evident  to 
any  one  reading  the  descriptions  of  Heineke's  cases  of  corrosive 
sublimate  kidneys — that  the  lesion  is  associated  from  the  start 
with  considerable  serous  oedema ;  he  attributes  this,  however,  to 
a  non-inflammatory,  increased  capillary  permeability,  and  pos- 
sible lessened  resorption,  analogous  to  the  amyloid  kidney,  and 
bases  this  view  on  the  absence  of  hyperaemia  and  hemor- 
rhages. 

It  is  difficult  to  follow  this  attempt  of  a  finer  classification  in 
either  substance  or  form.  In  reading  over  the  careful  work 
of  Heineke  on  the  subject,  it  appears  that  the  lesion  presents  it- 
self primarily  as  a  marked  parenchymatous  degeneration  with  in- 
flammatory oedema,  followed  soon  by  a  cellular  exudate  and  later 
by  productive  interstitial  changes.  To  sharply  separate  the 
primar}^  parenchymatous  degeneration  from  the  accompanying 
oedema,  and  again  the  almost  immediately  following  cellular 
exudate,  seems  to  me  somewhat  forced,  and  based  on  theoretical 
considerations,  which  are  open  to  some  criticism.  Who,  for 
instance,  in  the  inflammations  of  the  lung,  would  regard  the 
initial  oedema  which  precedes  the  cellular  exudate  as  non- 
inflammator}',  and  genetically  unrelated  to  it? 

The  absence  of  general  hypersemia  and  hemorrhages  cannot 
be  taken  as  proof  against  the  inflammator}'  character  of  the 


i)i-:(;iv\i:iv' \'i'i\K  and   i:xri)A'i'i\i':   kkatcrks  of  XKi'iiHriis  47 

lesion,  inasmuch  iis  any  inflann^d  or^an  with  nmcii  swelling  and 
infl;iinni:it()ry  (rdcnia  of  lis  });ir1s,  is  jrenerally  anaemic,  l-'iu'thcr- 
nioro,  it  apjx'ars  from  Ilcineke's  description  that  in  earh'  cases 
"  the  coi-tic.'il  cnpilhiries,  the  lilomerulnr  tufts,  .'ind  tlie  mechiUarA^ 
capillnrics  showed  fnujuent  abundant  hlood  injection."  (See 
])articul;niy  his  Case  1  of  seven  hours:  '^  The  glomeruli  dark  red, 
eciually  the  peri{)heral  ])ortions  of  the  pyramids."^)  I  can 
interpret  this  only  as  an  inflammatory  hypersemia.  This,  of 
course,  becomes  lessened  and  more  irre<2;ular  as  swellin<i;  and 
inflammatory  (rdema  progress.  Further,  it  is  no  a  priori 
certainty  that  the  appearance  of  the  cellular  exudate  depends 
only  upon  chemotactic  action  of  necrotic  cellular  masses. 
Other  factors  may  enter  into  this,  the  discussion  of  which,  how- 
ever, would  lead  us  too  far  from  our  topic. 

I  feel  unconvinced,  therefore,  that  we  are  justified  in  estab- 
lishinf»;  an  independent  category  of  nephroses  or  parenchy- 
matous degenerations  independent  of  inflammations,  as  Miiller 
would  have  it.  Indeed,  even  Marchand  is  quite  con- 
scious of  the  additional  difficulty  thus  introduced,  for  it 
would  still  become  necessary  to  again  apply  qualifying  adjec- 
tives. How  much,  for  instance,  would  be  gained  by  speaking 
of  parenchymatous  or  degenerative  nephrosis  or  of  an  inflamma- 
tory nephrosis?  The  latter,  particularly,  would  soon  lead  back 
to  a  confusion  from  which  we  are  only  too  anxious  to  escape. 

We  will  therefore  not  recognize  in  our  study  a  non-inflam- 
matory, parenchymatous  degeneration. 

Now,  to  return  to  the  discussion  of  simple  nephritis:  It  is 
the  form  which  is  most  frequently  found  in  connection  with  all 
types  of  fevers,  such  as  typhoid  fever,  the  early  stages  of  scarlet 
fever,  synanche  infections,  cholera,  septicaemia,  and  others.  It 
also  occurs  in  toxic  and  cachectic  states  and  in  some  poisonings. 

Such  a  kidney,  grossly,  varies  little,  if  any,  from  the  normal 


48  bright's  disease 

in  size,  luit  appears  swollen.  The  capsule  is  stretched  thin,  but 
can  be  stripped  off  with  ease.  The  surface  bulges,  and  this  can 
frequently  l^e  seen  under  the  thin  capsule ;  it  is  smooth,  and  has 
usually  a  sort  of  dusky-gray,  pinkish  color. 

That,  however,  is  open  to  some  variations :  Occasionallj^,  the 
surface  may  show  distinct  areas  of  vascular  injection,  but  on 
account  of  the  pressure  of  the  swollen  and  oedematous  par- 
enchyma, the  superficial  veins  are  usually  not  at  all  prominent, 
and  sometimes  cannot  be  made  out  at  all.  Again,  they  may 
appear  more  prominent  in  places,  and  lost  in  others,  on  account 
of  unequal  distribution  of  inflammatory  changes  and  consequent 
compensatory  changes  in  the  blood-stream.  On  section,  the 
kidney  shows  conditions  similar  to  those  observed  on  gross  ex- 
amination. The  cortex  always  bulges  and  appears  relatively 
prominent.  The  markings  show  irregularities  and  the  glomeru- 
lar rows,  instead  of  presenting  a  very  definite  arrangement,  are 
distorted.  The  glomeruli  appear  in  spots  very  prominent  on 
account  of  a  very  marked  vascular  injection,  and  in  others  they 
may  have  disappeared  altogether,  or  they  can  be  recognized  in 
the  form  of  fine,  grayish,  slightly  elevated  points.  They  seem 
to  be  raised  over  the  surface  of  the  cortex.  Such  rows  of  glom- 
eruli are  separated  by  thick,  grsij,  swollen,  tubular  masses. 
Occasionally,  one  can  squeeze  from  the  kidney  a  certain  amount 
of  oedematous  fluid;  this,  however,  depends  entirely  upon  the 
amount  of  serous  exudate.  Where  all  of  this  has  been  imbibed 
by  the  structures  of  the  kidney,  it  may  even  be  dry  and  firm. 

Similar  conditions  prevail  in  the  medulla.  The  medulla, 
instead  of  appearing  clear  and  definitely  striated,  is  rather  dull, 
grayish,  swollen.  The  medullary  rays  are  prominent,  pale,  and 
oedematous,  while  the  interpolated  vessels  are  for  this  reason 
obscured  or,  for  compensator}^  reasons,  appear  in  places  much 
more  prominent  than  the}'  ordinarily  do    (Fig.    1).     Pressing 


^- , 


Fig.  1. — Nephritis  simplex,  from  general  septicaemia  following  middle-ear  disease. 
Cloudy  swelling  and  serous  exudate.  Some  of  the  glomerular  rows  with  inflammatory 
engorgement,  but  generally  the  cortical  markings  lost  or  disturbed  by  cloudy  swelling  and 
serous  exudation  into  the  parts.  Similar  state  in  the  medulla.  Microscopically,  this 
kidney  showed  no  cellular  or  fibrinous  exudation,  but  cloudy  swelling  of  cells,  swelling  of 
glomerular  endothelium  and  epitheliimi,  and  serous  exudate  into  the  glomerular  capsule 
and  interstitial  tissue.     Weight,  250  gms. 


DEGENERATIVE    AND    EXUDATIVE    FEATURES    OF    NEPHRITIS      49 


^1 

;  ^'i 

'- 

1 ' 

9 

Fig.  2. — Xephritis  .simplex:  Inflammatory  engorgement  of  glomerular  capillaries,  with 
general  enlargement  of  the  tuft,  cloudy  swelling  of  its  endothehum  and  epitheUum;  the 
latter  partly  desquamated.  Granular  disintegration  of  the  capsular  epitheUum.  Occa- 
sional engorgement  of  intertuluilar  capillaries.  Cloudy  swelhng  and  granular  cUsintegra- 
tion  of  tubular  cells,  wiih  occasional  nuclear  degeneration. 


DEGEXERATni-]    AND    EXUDATH  E    FEATURES    OF    NEPHRITIS  51 

<»;ently  on  the  medulla  toward  the  pelvis,  we  are  frequently  able 
to  dis('liai;ii(^  from  the  papillae  a  sli*ihtly  turhid  fluid,  and  on 
examination  that  fluid  is  found  to  consist,  to  threat  extent,  of  des- 
quamated tul)ular  epithelium.  This  leads  us  to  the  microscopic 
appearances. 

We  observe,  here,  certain  variations  from  the  normal,  which 
are  more  or  less  evenly  distributed  throu<ihout  the  whole  kidne}' 
substance.  In  the  simplest  and  earliest  forms,  the  more  promi- 
nent features  are  turbidit}'  of  the  ,ulomerular  tuft,  serous  exuda- 
tion into  the  glomeruli,  and  a  parenchymatous  degeneration  of 
the  epithelium  of  the  convoluted  tubules.  The  "ilomerular  capsule 
appears  usually  quite  large,  and,  in  the  well-established  cases, 
surrounded  by  oedematous  tissue.  The  epithelium  of  BowTnan's 
capsule  is  turbid,  and  so  is  the  epithelium  which  is  reflected  over 
the  glomerulus.  In  a  certain  number  of  glomeruli  the  capillar}' 
tuft  is  very  markedly  injected;  in  others,  inflammatory  swelling 
and  turbidity  of  the  capillary  endothelium  evident  and  soon 
foUow^ed  by  a  serous  exudate,  so  that  the  glomerular  tufts  appear 
thick  and  plump  and  fill  the  capsule.  In  this  way  glomeruli 
gradually  lose  their  hyperaemic  form.  Then  a  serous  exudate, 
demonstrable  l)y  its  coagulating  on  hardening,  can  be  seen  in 
BowTuan's  capsule.  If  that  exudate  assumes  any  marked  degree, 
the  tuft  is  compressed  by  it,  and  thus  its  circulation  necessarily 
much  interfered  with.  If  this  process  assumes  any  dimensions, 
the  capsule  becomes  dilated,  while  the  tuft  itself  is  further  pressed 
against  one  part  of  the  capsule,  usually  at  the  entrance  of  the 
vessels;  such  glomeruli  appear  then  as  the  fine,  slightly  elevated, 
pale,  granular  dots,  noticeable  on  the  cut  surface  of  the  cortex 
(Figs.  2  and  3). 

In  the  majority  of  cases  of  simple  nephritis  that  point 
is  not  reached,  at  least  not  in  the  majority  of  glomeruli,  and  they 


52  bright's  disease 

remain  turbid,  swollen,  and  the  capillary  walls  thick,  pale,  and 
plump. 

The  changes  in  the  epithelial  cells  of  the  convoluted  tubules 
are  more  evident  at  first  sight  than  the  changes  found  in  the 
Malpighian  corpuscles.  They  consist  of  varying  degrees  of  par- 
ench3^matous  degeneration  (Fig.  4).  The  nature  of  parenchy- 
matous degeneration  is  in  itself  a  very  important  and  fundamen- 
tal study  of  general  pathology.  I  take  it  that  you  are  familiar 
with  the  essential  features  of  it  from  your  previous  studies. 
But  it  may  not  be  amiss  if  I  shortly  summarize  once  more  for 
you  the  present  knowledge  regarding  it. 

The  kidney  from  the  time  of  Virchow  ^  has  been,  above  all 
others,  the  favored  organ  for  investigations  into  the  character  of 
parenchymatous  degeneration.  Virchow,  whose  ideas  on  its 
nature  I  have  already  presented,  introduced  the  appropriate 
descriptive  term  of  ''cloudy  swelling";  and  these  two  words 
express  well  its  appearance.  Such  cells  lose  their  definite  normal 
structures  and  outline.  The  delicate,  rod-like  striation,  com- 
posed of  a  regular  arrangement  of  fine  granules  (Altmann's 
granules),  which,  as  you  remember,  forms  a  feature  of  the  pro- 
toplasm of  the  cells  of  the  convoluted  tubules,  becomes  dis- 
turbed, irregular,  the  granules  more  numerous,  coarser,  and  more 
prominent;  the  cell  as  a  whole  appears  darker.  The  finely 
brushed  extremity  may  be  lost.  The  cell  enlarges,  appears 
succulent,  swollen,  turbid,  and  plump,  and  occasionally  as  if 
dusted  with  granules.  This  has  given  rise  to  the  term  "  granular 
degeneration. ' '  These  granules  are  insoluble  in  chloroform,  ether, 
and  alcohol,  but  soluble  in  acetic  acid  and  weak  alkalis,  and 
have  therefore  been  regarded  as  of  an  albuminous  character. 
There  may  be  present,  however,  other  larger,  hyaline,  globular 
bodies,  lliey  are  regarded  by  some  as  the  product  of  a  path- 
ological secretion.     I  shall  say  more  about  these  in  the  discus- 


DEGENERATIVE    AND    EXUDATIVE    FKATIHES    OF    NEPHRITIS  53 


fJ^' 


r 


\ 


«>I 

V,    ^ 

V.** 

«>' 

A 

i^ 

';•'•'• 
•? 

L 

i 

\% 


« 


Fig.  3. — Nephritis  simplex:  Glomerular  capsule  distended  by  serous  exudate.  The 
tuft  compressed  and  adherent  to  part  of  the  capsular  wall,  whose  epitheUum  is  relatively 
well  preserv'ed;   cloud j'  swelling  and  oedema  of  surrounding  structures.     X  210. 


^•» 

'   f^''^^' 

^^§ 

♦1-- 

^ 

'       >     . 

« 

0 

9r 

^^f^ 

^^ 

/  • 

\     ^ 

♦  ; 

i 


r 

9    Z-^ 


J^^^^    .,,'.•?. 


o 


y*j 


Fig.  4. — Granular  disintegration  of  convoluted  tubules.     A  better  preserved  loop  of  Henle. 


DEGENERATIVE    AND    EXUDATIVE    FEATURES    OF    NEPHRITIS   55 

sioii  of  tube-casts.  The  nucleus  is  priniaril>'  unaffected,  and  is 
involved  only  in  progressive  and  severe  lesions.  Its  chan<!;es  are 
those  of  chromatoh'sis,  i.  e.,  a  centrifugal  loss  of  chromatic  sub- 
stance, and,  as  Benario*^  holds,  are  similar  to  those  observed 
within  the  protoplasm.  The  outcome  of  this  form  of  degenera- 
tion varies.  In  the  simple  nephritis,  when  the  nucleus  is  not 
destroyed,  restitution  to  integrity  is  probably  the  rule,  /.  e., 
the  majority  of  cells  recover.  Others,  however,  may  go  on  to 
complete  destruction,  the  cell  membrane  becomes  lost,  and  the 
protoplasm  disintegrates  into  a  granular  detritus  and  dissolves. 
When  such  severe  changes  are  absent,  but  the  parenchymatous 
destruction  continues,  the  appearance  of  fatty  substances  be- 
comes pronounced.  I  shall  leave  the  discussion  of  this  subject  to 
a  later  date,  when  we  are  dealing  with  the  fatty  type  of  nephritis. 

Opinions  about  the  nature  of  parenchymatous  degeneration 
differ  widely.  It  involves  two  main  questions:  What  is  the 
derivation  and  significance  of  the  granules,  and  what  the  origin 
and  significance  of  the  swelling  of  the  affected  cells? 

Both  were  easily  explained  by  Virchow's  conception  of  over- 
nutrition  of  the  cells.  Only  shortly  before  his  death  Virchow 
declared :  The  swelling,  as  well  as  the  cloudiness,  depend  upon  a 
permanent  assimilation  of  soluble  substances,  which  are  pre- 
cipitated within  the  cell  and  undergo  further  changes.  The 
swelling  is,  therefore,  not  caused  by  the  usual  nutritive,  but 
by  changed  material." 

An  entire  change  in  these  ideas  went  necessarily  with  those 
of  the  character  of  inflammation,  for  inasmuch  as  the  parenchy- 
matous degeneration  was  no  longer  considered  a  nutritive  dis- 
turbance, but  the  direct  result  of  an  injury,  it  became  necessary 
to  explain  the  cloudy  swelling  in  some  other  way. 

It  has,  therefore,  been  variously  considered  either  as  a 
granular    precipitation    of    normally    dissolved    proteid    (Rind- 


56  bright's  disease 

fleisch/^  Cohnheim^),  or  as  a  coagulation  (Klebs^"),  or,  more 
generally,  as  a  disorganization  of  protoplasm  with  resorption  of 
fluid  (Ziegler  ^\),  or  as  a  regressive  metamorphosis  due  to  under- 
nutrition (Thoma^^).  Some,  like  Birch-Hirschfeld  ^^  and  von 
Recklinghausen,^^  retain  partly  the  views  of  Virchow.  The 
former  believes  that  it  represents  an  accumulation  of  undis- 
solved or  precipitated  proteids  as  the  result  of  increased  proteid 
destruction  with  an  increased  supply  of  proteid;  the  latter 
regards  it  as  an  increased  functional  activity  similar  to  the 
increased  production  of  mucus  in  the  catarrhal  inflammations  of 
mucous  membranes. 

Considerable  experimental  work  on  the  subject  has  been  done. 
Schilling  ^^  obtained  cloudy  swelling  of  one  kidney  forty-eight 
hours  after  tying  the  renal  vein  of  the  other.  He  concludes, 
therefore,  that  this  must  be  the  result  of  compensatory  action  on 
part  of  that  kidney,  caused  by  the  increased  amount  of  urinary 
constituents  in  the  blood,  a  forerunner  of  hypertrophy.  Land- 
steiner,^^  however,  has  pointed  out  that  these  results  are  not 
identical  with  those  of  infections  or  intoxications.  The  cells  of 
the  flrst  convoluted  tubules  were  left  entirely  free,  and  the  lesion 
remained  strictly  localized  to  the  cells  of  the  proximal  convo- 
luted tubules.  This  is  the  very  opposite  from  what  is  usually 
observed  in  disease. 

Such  experiments  are  entirely  unconvincing  for  explana- 
tions of  either  hypertrophy  or  parenchymatous  degeneration, 
for  the  reason  that  such  an  interference  suddenly  produces 
marked  complications  in  the  functions  of  the  other  kidne}'',  and 
to  such  an  extent  that  one  is  not  justified  in  drawing  any  con- 
clusions from  it.  One  might  interpret  these  results  as  moderate 
injury  to  a  particular  group  of  cells  of  the  kidney,  caused  by  the 
sudden  changes  in  circulatory  conditions  and  the  increased 
amount  of  urine  constituents.     There  is  no  evidence,  as  far  as  I 


DEGENERATIVP]    AND    KX1M)ATIVK    FEATrUKS    OF    NEPHRITIS  57 

know,  \\liicli  could  conohofate  the  view  that  parenchymatous 
de<!;enei'ation  heai's  a  ,i;enetic  rehition  to  liypertrophy. 

'rh(M'e  is  no  uniformity  of  opinion  about  the  derivation  of  the 
jj;ranules.  While  some  look  upon  them  as  an  increase  of  the 
normal  type,  Galeotti '"  holds  that  they  represent  a  different 
a,i;«;re.i;ate  condition  of  the  cytoplasm,  while  the  normal  <^ranules 
disappear.  Based  on  Naegeli's  theory  of  protoplasm,  he  holds 
that  the  proteid  molecules  lose  their  ability  for  the  formation  of 
micellae,  which  are  the  fundamental  requisite  of  life,  and  the 
new  granules  thus  resulting  represent  the  first  evidences  of  cell 
necrosis. 

It  will  be  seen  that  views  about  parenchymatous  degenera- 
tion are  largely  dependent  upon  the  theoretical  conceptions  of 
protoplasm.  This  is,  perhaps,  best  illustrated  in  the  most  recent 
ideas  of  Albrecht,'"*  who  regards  protoplasm  as  an  emulsion, 
which,  under  various  influences,  particularly  water,  loses  its 
homogeneity,  and  changes  to  a  mechanical  mixture  which  con- 
tains drops  of  one  substance  suspended  in  the  other  (tropfige 
Entmischung). 

Based  on  his  own  studies,  Landsteiner  ^^  concludes  that  the 
process  is  essentially  a  destruction  of  the  filamentous  structure 
of  the  protoplasm  with  clumping  into  granules.  The  swelling  is 
to  be  attributed  to  the  destruction  of  the  protoplasm.  He  is 
inclined  to  attribute  the  whole  to  autolytic  processes.  Similar 
are  the  views  of  Orgler  and  others,  who,  having  found  substances 
of  the  myelin  group  in  such  cells,  look  upon  it  merely  as  a  myelinic 
degeneration,  or,  better,  disorganization  of  the  protoplasm 
— an  autolysis.  I  shall  say  more  about  this  later  in  connection 
with  the  fatty  types  of  nephritis. 

Adami  ^°  holds .  to  the  possibility  of  increased  absorption  of 
food-stuflfs,  with  imperfect  conversion  and  utilization  of  the  same, 
and  differentiates  it  distinctly  from  granular  degeneration  or  the 


58  bright's  disease 

*' tropfige  Entmischung "  of  Albrecht.  This  he  regards  as  a 
disintegrative  condition  of  the  cytoplasm,  an  indication  of  cell 
death,  and  allied  to  the  granular  degeneration  described  by 
Verworn  in  injured  infusorians. 

From  my  own  observations  I  believe  that  the  process  de- 
pends upon  outside  influences  which,  either  by  excessive  stimu- 
lation of  the  cell  activity,  or  by  direct  harmful  influences,  pro- 
duce disturbances  in  the  composition  of  the  protoplasm  which 
necessarily  lead  to  changes  in  the  organization  of  the  parts,  and 
temporary  or  permanent  cell  injury.  The  appearance  of  the 
granules  I  also  regard  as  an  indication  of  changed  protoplasmic 
constitution,  whereby  the  normal  composition  and  arrangement 
are  gradually  lost;  and  I  attribute  the  swelling  to  the  thus 
altered  physical  conditions  of  the  cell  and  its  changed  environment. 
Depending  on  the  degree  of  injury  and  the  correlated  disturbances 
in  the  protoplasm,  the  cell  either  adapts  itself  to  the  new  environ- 
ment or  changes  its  character  entirely  by  undergoing  further 
degenerative  (fatty)  changes  or  complete  disorganization. 

I  have  endeavored  to  recall  to  your  mind  these  fundamental 
principles  of  general  pathology  because  they  play  so  important 
a  role  in  the  correct  and  clear  conceptions  of  nephritis,  and  we 
will  have  to  refer  to  them  frequently  in  our  subsequent  study. 

To  return  to  the  subject  of  simple  nephritis,  I  shall  only  have 
to  add  that  the  tissue  between  the  tubules  shows  the  same  in- 
flammatory oedema  which  I  have  already  mentioned  in  connec- 
tion with  the  periglomerular  tissue.  It  is  stretched,  hazy, 
separated  by  oedematous  fluid.  The  intertubular  capillaries  are 
in  parts  engorged  or  may  be  compressed. 

The  result  of  simple  nephritis  is  restitution  to  integrity  in  the 
majority  of  cases.  The  inflammatory  oedema  subsides  and,  after 
clearing  of  the  lymphatics,  is  resorbed;  the  glomeruli  and  the 
vascular  apparatus,  not  having  undergone  permanent  injury, 


DEGENERATIVE    AND    EXTDATIVE    FEATURES    OF    XEPIIRITIS   59 

assume  their  former  condition.  The  epitheHum  also  regenerates 
rapi(ll>',  inastnuch  as  only  little  of  it  has  undergone  actual  necro- 
sis, and  the  kidney  may,  therefore,  be  said  to  recover  completely, 
unless  conditions  supervene  which,  prolonging  the  interference, 
gradually  lead  to  the  more  severe  types  of  kidney  inflammations 
which  I  am  now  about  to  describe. 

Before  that,  however,  a  few  words  al^out  the  functional 
changes  in  these  cases  of  simple  nephritis.  The  structural 
changes  in  the  vascular  apparatus,  as  well  as  the  mechanical 
conditions  in  the  swelling  of  the  parts,  result  necessarily  in  a 
much  diminished  amount  of  urine,  of  relatively  high  concentra- 
tion and  specific  gravity,  high  colored — the  typical  so-called 
fever  urine.  Serum-albumin  is  usually  present,  and,  depending 
upon  the  amount  of  inflammatory  oedema  into  glomeruli  and 
tul^ules,  never  more  than  in  traces.  In  morphotic  elements  this 
urine  is  poor,  as  the  process  never  leads  to  extensive  loss  of 
cellular  elements,  and  the  exudate,  as  we  saw,  is  purely  serous. 
The  first  indication  of  recovery  is  rapid  increase  in  the  amount 
of  urine,  which  indicates  clearing  of  lymphatics  and  capillary^ 
engorgement;  with  return  to  physiological  functions,  albumin 
disappears  and  the  urine  loses  its  increase  in  concentration. 

Closely  allied  to  nephritis  simplex  is  a  type  which  is 
characterized  not  only  by  parenchymatous  degeneration  and 
inflammatory  oedema,  but  by  a  marked  desquamation  of 
epithelium  and  excessive  proliferation  of  the  same.  To  this 
subdivision  the  term  nephritis  prolifera  might  properly  be  given 
as  distinguishing  it  from  the  simple  form.  It  was  called  by 
Virchow  the  catarrhal  form  of  nephritis;  later  it  was  much 
neglected,  but  recognized  by  Orth  ~^  and  Kaufman  "  as  desqua- 
mative and  proliferative  papillary  catarrh  on  account  of  its 
predominating  appearance  in  the  medulla  of  the  kidney.  In  this 
form  we  may  squeeze  out,  at  autopsy,  an  abundance  of  turbid 


60  bright's  disease 

fluid  from  the  medulla,  consisting  of  epithelial  cells  and  detritus. 
It  is,  however,  by  no  means  confined  to  these  tubules,  but  occurs 
diffuse,  as  recent  investigations  of  others  and  my  own  have 
shown ;  it  is  seen  particularly  in  cases  when  the  parenchymatous 
degeneration  of  the  epithelium  is  marked,  and  much  of  it 
destroyed  and  lost.  It  may,  therefore,  become  associated  with 
all  other  types  of  nephritis,  and  plays,  as  I  presently  hope  to 
show,  much  more  of  a  role  in  the  inflammatory  process  than 
is  usually  supposed  (Fig.  5).  While  Virchbw  had  observed  the 
desquamation  of  the  epithelium,  it  was  shown  by  Beer  in  1859 
that  these  cells  rapidly  and  excessively  proliferated,  that  the 
tubules  dilate  and  are  frequently  filled  with  these  cell  masses. ^^ 
He  regarded  this  lesion  as  an  inflammatory  phenomenon. 

Later  observers,  hke  Weigert,-^  Golgi,^^  and  others,-^  studied 
these  cell  types  more  carefully  and  described  the  formation  of 
epithelial  giant-cefls  in  nephritis  (Fig.  6).  But  the  idea  gained 
ground  that  they  represented  either  true  regenerations,  or,  at 
least,  regenerative  attempts  with  failure.  The  studies  of 
Arnold  -'  and  Baumgarten^^  on  the  formation  of  tubercles  in  the 
kidney  connected  this  proliferation  more  definitely  with  the 
defenses  of  the  tissue  against  the  tuberculous  invasion,  and  my 
own  studies  in  the  matter  have  convinced  me  -^  that  we  have 
here  before  us  a  type  of  parenchymatous  inflammator}^  reaction 
analogous  to  the  excessive  epithelial  proliferation  in  certain 
other  inflammations;  for  instance,  in  the  lungs,  in  catarrhal 
pneumonia.  I  was  led  to  this  view  because  of  the  predominance 
of  an  irregular  cell  activity  and  atypical  cell  forms,  to  which  we 
cannot  attribute  any  normal  restitution  or  normal  activity,  the 
formation  of  syncytial  giant-cells,  and  the  excessive  intracanalic- 
ular  proliferation.  The  latest  observations  of  Heineke^"  on 
the  kidney  changes  in  corrosive  sublimate  poisoning  have  brought 
corroboration  of  this  contention,  for  he  too  observed  the  same 


DEGENERATIVE    AND    EXUDATIVE    FEATURES    OF    NEPHRITIS  61 


Fig.  0. — Xepliritis  prolifera  et  productiva:  Parts  of  Henle's  loops  filled  and  dilated 
witli  newly  formed  cells,  recognizable  by  their  size,  shape,  protoplasm,  and  richly  chromatic 
nuclei.  One  very  large  convoluted  tubule  filled  with  necrotic  cell  masses,  a  smaller  one 
above.     The  intervening  fibrous  tissue  thickened.      X  360. 


& 


Fig.  6. — Formation  of  multinuclear  giant-cell  in  a  convoluted  tubule. 


DKdKNKHA'rn'K    AM)     KXlDATni-:    FIOATl'RES    OF    NEPHRITIS  63 

(liffiise,  excessive  epithelial  proliferation.  These  cells,  moreover, 
were  distinctly  phaj»;ocyti('  to  the  necrotic  cell  masses.  In  this 
way  several  o;enerations  of  epithelial  cells  were  produced,  dis- 
integrated, and  eliminated  before  true  permanent  regeneration 
commenced.  The  epithelial  proliferation  in  nephritis  is,  then, 
an  inflammatory  phenomenon,  and  should  be  appreciated  as  an 
important  factor  in  the  pathogenesis  of  the  inflammation. 

Functionally  the  lesion  becomes  evident  by  the  free  discharge 
of  the  newly  formed  and  desquamating  cell  masses  and  epithelial 
detritus  in  the  lu'iiie.  This,  therefore,  is  richer  in  morphotic 
elements.  Microscopic  examination  shows  these  cells  in  a  free 
state,  when  they  are  frequently  mistaken  for  leukocytes,  or  in 
the  form  of  cellular  or  granular  casts. 

This  leads  directly  to  the  important  and  severe  kidney  in- 
flammations, which  I  group  under  the  category'  of  nephritis 
degenerativa  et  exudativa.  As  the  name  and  its  adjectives 
imply,  we  include  here  types  in  which  either  the  degenerative  or 
the  exudative  features  predominate,  or  in  which  both  appear  so 
intense  and  characteristic,  and  lead  to  such  permanent  alterations 
in  the  organ,  that  ciuantitativety  and  qualitatively  they  go  far 
beyond  the  lesions  of  simple  and  proliferative  nephritis. 

It  is  in  these  complicated  forms  of  nephritis  particularly  that 
opinions  differ  widely  as  to  pathogenesis  and  histogenesis.  I 
have  already  sketched  in  the  introductory  lecture  the  funda- 
mental questions  which  are  involved,  but  it  is  necessary  here 
that  some  attention  be  paid  at  least  to  the  more  important 
details  of  the  discussion. 

You  will  remember  from  my  first  lecture,  and  from  what  I 
said  in  the  beginning  to-day,  that  modern  pathologists  are 
divided  into  several  camps  as  regards  the  conception  and 
definition  of  inflammation. 

One  group  adheres  to  the  old  term  of  parenchymatous  in- 


64  bright's  disease 

flammation.  Aschoff,  for  instance,  in  his  new  book  on  patho- 
logical anatomy,  states :  "  As  long  as  cloudy  swelling  of  the  tu- 
l3ular  epithelium  controls  the  picture  of  the  inflammatory  reac- 
tion without  particular  change  in  the  vascular  connective  tissue 
and  the  glomerular  bodies,  one  is  justified  to  speak  of  a  tubular 
nephritis."  The  parenchymatous  degeneration  is  taken  as  the 
result  of  an  inflammatory  reaction  and  represents  a  condition  of 
increased  secretion  with  increased  formation  of  protoplasmic 
granules,  colloid  and  fluid  drops,  and  vacuoles.  Exudative 
processes  are  looked  upon  either  as  an  accompaniment  or  result 
of  the  epithelial  irritation. 

This  view  has,  as  you  see,  a  relation  to  the  old,  previously 
discussed  ideas  of  Virchow  on  parenchymatous  degeneration  and 
inflammation.  But  it  differs  from  them  essentially  in  regarding 
the  parenchymatous  degeneration  as  an  active  process,  the  direct 
result  of  an  injury  which  is  followed,  and  not  caused,  as  Virchow 
would  have  it,  by  exudation.  Parenchymatous  inflammation  is, 
therefore,  the  prototype  of  an  inflammation;  only  when  the 
epithelium  is  killed  the  inflammation  becomes  modified. 

A  second  group  restricts  the  inflammatory  conception  solely 
to  the  vascular  and  exudative  reactive  changes,  and  divorces  the 
degenerative  features  absolutely  from  them.  These  latter  may, 
in  the  minds  of  some,  either  precede  and  excite  the  inflammatory 
changes  (Marchand,  I.  c),  or  they  may  initiate  and  cause  a 
degenerative  parenchymatous  involvement. 

Xauwerck'^^  has  come  out  particularly  strong  for  the  latter 
view  in  nephritis  in  an  attempt  to  disprove  Weigert's  conceptions, 
Ijut  von  Kahlden ""  properly  remarks  that  in  an  extensive  study 
he  has  never  met  such  cases. 

A  third  group,  finally,  holds,  to  quote  with  Lubarsch,  that 
only  the  combination  of,  and  intimate  correlation  of,  alterative, 
exudative,  and  proliferative  changes  constitute  inflammation. 


l)H(iK\KI{.\TTVK    AXD    70XrT)AT(\'K    FKA'ITHKS    OV    XEPHTUTIS   Of) 

'lliis  iiioup  of  i  1 1  vesti^'ators  eliminates  entirely  from  the  infiam- 
m.'ilory  coiicc))!  ion  the  (l(\a;('iH'r;it  ix'c  parenchymatous  processes, 
and  does  not,  t hei'efoi'e,  tolei-atc  the  so-called  parenchymatous 
inflammations  of  the  oldei-  wi'iters.  Tt  rejects,  for  instance, 
entii'ely  the  term  of  parenchymatous  myocarditis,  neuritis, 
myelitis,  and  so  forth.  It  denies  the  inflammatory  character  to 
purely  nutritive  and  alterative  chanj^es  in  the  parenchyma, 
unless  combined  with  exudative  and  proliferative  chang-es. 

It  is  this  ,<;rou})  of  investigators  which  would  separate,  in  the 
case  of  the  kidney,  as  we  saw  in  the  ljeginnin<^  of  this  lecture,  a 
non-inflammator}"  parenchymatous  degeneration  as  an  essential, 
but  not  a  nephritic,  lesion. 

One  can  recognize,  therefore,  various  attempts  of  classifica- 
tion on  the  part  of  investigators : 

1.  Degenerative  changes  in  the  parenchyma  form  the 
essential  feature  of  nephritis;  and  they  may  or  may  not  be 
accompanied  or  followed  by  vascular  exudation. 

2.  Vascular  exudation  is  the  characteristic  phenomenon  of  a 
nephritis:  ia)  This  may  or  may  not  become  associated  with 
degenerative  changes  in  the  parenchyma,  (b)  It  depends  upon 
the  parenchymatous  destruction,  (c)  It  may  involve  the  whole 
vascular  apparatus  of  the  kidney  or  only  parts  of  it  (glomerulo- 
nephritis) . 

3.  All  established  inflammatory  affections  of  the  kidney  are 
diffuse;  that  is,  they  involve  all  the  structures  (parenchymatous 
and  ^'ascular)  of  the  organ,  although  they  may  be  une^•enly 
distributed.  An  absolute  dependence  of  one  change  upon  the 
other  cannot  be  made  out,  although  at  the  beginning  either 
degenerative  or  exudative  features  of  the  process  may  appear 
more  prominent,  and  in  a  number  of  cases  may  continue  so. 

This  latter  standpoint  appears  to  me  the  most  acceptable  one, 
with  the  following  qualifications: 


66  bright's  disease 

(A)  The  term  inflammation  comprises  the  sum  total  of  those 
correlated  l3ut  not  absolutely  dependent  degenerative,  prolifer- 
ative, and  exudative  changes  which  are  the  direct  result  of  an 
injuiy  to  a  part.  Pure  degenerative  and  proliferative,  as  well  as 
pure  exudative,  inflammations  do  not  exist,  although,  for  reasons 
to  be  discussed  later,  one  of  these  inflammatory  attributes  may 
become  much  more  pronounced  and  prominent  than  the  others. 

{B)  A  confinement  of  an  inflammatory  lesion  to  a  particular 
portion  of  the  kidney  substance — for  example,  glomeruli — does 
not  exist,  so  that  the  term  glomerulonephritis  is  wrongly  used  in 
such  a  sense.  On  the  other  hand,  although  there  is  no  kidney  in- 
flammation in  which  glomerular  changes  are  lacking,  yet  there 
is  no  proof  that  this  lesion  is  the  starting-point  of  all  cases  of 
nephritis. 

(C)  I  therefore  include  the  degenerative  features  as  inflam- 
matory phenomena,  and  regard  them  as  evidences  of  an  injury, 
or  the  passive  features  of  an  inflammation,  contrasted  with  the 
proliferative  and  exudative  reactive  phenomena  of  the  process. 
But  the  close  association  and  relation  l^etween  the  passive 
degenerative  and  reactive  proliferative  parenchymatous  and 
exudative  changes  make  it  impossible  in  my  mind  to  ever  sep- 
arate them,  the  one  as  non-inflammatory,  the  other  as  inflamma- 
toiy.  Pure  parenchymatous  degenerative  lesions,  unaccom- 
panied b}^  at  least  an  inflammatory  oedema  of  the  parts,  do  not 
exist,  and  it  is  an  artificial  stretching  of  ideas  to  keep  them 
distinct  from  the  conceptions  of  the  inflammatory  process. 
This  conception  of  inflammation  is,  therefore,  not  that  of  a  single 
either  purely  passive  (Virchow)  or  purely  reactive  (modern) 
process,  but  an  expression  of  the  sum  total  of  genetically  related, 
partly  injurious  and  partly  helpful,  processes,  which  are  excited 
])y  irritants.* 

*Compare  Zioglcr,  rdjcr  don  froscnwurtigcn  Slund  dci   Lchre  von  dor  Entzi'indung, 
Deutsche  Klinik,  xi. 


DEGENERATIVE    AM)    EXUDATIVE    FEATURES    OF    NEPHRITIS  67 

Other  conceptions  suffer,  in  my  opinion,  from  the  inherent 
weakness  and  artificiahty  of  too  strict  classification. 

Followinii-  the  oriiiinal  description  ))y  Klebs  of  <^'lomerulo- 
nephritis,  it  h:is  hccn  the  effort  of  many  to  estabhsh  this  as  a 
particular  characteristic  type  of  nephritis,  and  some,  like 
Friedliinder^'  and  Xauwerck,  have  ^one  so  far  as  to  speak  of 
<^-lomerulonephritis  only  then,  when  the  glomeruli  alone  are 
affected,  and  in  a  characteristic  inflammatory  thrombosis  of  the 
capillary  tuft. 

On  the  other  hand,  Ribbert  ^^  regards  glomerulonephritis 
as  the  starting-point  of  any  nephritis,  and  he  therefore  classifies 
an}'  further  changes  as  subdivisions  of  this  uniformly  primar}^ 
anatomical  lesion.  While  he  strictly  adheres  to  a  division  of 
parenchymatous  and  interstitial  nephritis,  he  interprets  them 
as  subdivisions  of  the  glomerular  affection. 

These  represent  rather  extreme  views,  and  in  my  opinion 
suffer  from  the  endeavor  to  create  types  of  nephritis  either  out 
of  stages  of  a  lesion,  or  from  an  undue  impression  with  prominent 
features  of  the  inflammatory''  process  in  certain  cases. 

Degenerative  and  exudative  nephrites  are  always  the  result 
of  intense  general  and  characteristic  intoxications  and  infec- 
tions; above  all,  the  acute  exanthemata,  particularly  during  the 
late  stages  of  scarlet  fever,  but  other  infectious  diseases  as  well, 
furnish  a  large  number  of  the  cases — the  severe  septic  condi- 
tion of  the  usual  or  specific  types,  septicaemia,  pysemia,  pneu- 
monia (the  latter  not  at  all  infrequently),  syphilis,  erysipelas, 
and  others.  Sometimes  the  primary  focus  of  infection  may  be 
difficult  to  detect,  or  may  appear  insignificant,  as  in  angina 
pharyngis,  tonsillitis,  or  purulent  otitis.  But  there  can  be  no 
doubt  that  severe  nephritis  may  be  either  associated  with  or 
follow  these  apparently  trivial  infections.  The  mouth  and  ear 
should  therefore  always  be  inspected  during  life  and  at  autopsy. 


68  bright's  disease 

Grossly  the  kidney  shows  the  conditions  of  simple  nephritis 
intensified.     It  is  laroer  than  normal,  firm,  buloing,   and  the 
surface  prominently  convex.     The  capsule  stretched,  removed 
with  ease,  leaves  a   smooth  surface,  with  an  opaque,   dusky, 
reddish-white    iiround-color,    and    numerous    irregular,    small, 
point-like   or   streaky   hemorrhages.     These   may   occasionally 
assume  such  dimensions  as  to  give  to  the  whole  kidney  a  pre- 
dominatingly hemorrhagic  appearance.    Sometimes  small  areas 
of  yellow  (fatty)  color  are  irregularly  distributed  (Fig.  7).     On 
section  the  kidney  is  juicy,   and  discharges  readily  a  turbid, 
oedematous  fluid.     The  cortex  is  enormousty  swollen,  pale,  and 
contains  irregular  hemorrhagic  streaks  and  dots.     The  normal 
glomerular  rows  have  apparently,  to  great  extent,  disappeared, 
l^ut  the  glomeruli  are  evident  in  the  form  of  glistening,  white, 
slightly  elevated  points  or  minute  granules.     The  intervening 
tubular  substance  appears  thick  and  cloudy.      The  line  of  de- 
marcation between  cortex  and  medulla  is  unusually  well  marked, 
by  a  more  prominent  but  diffuse  pinkish-gray  (cyanotic)  ap- 
pearance of  the  medullary  portion.     Here  also  a  grayish  sweUing 
with  obliteration  of  the  normal  rays  is  marked.     These  are  the 
evidences    of    the    well-established   forms;  and    naturally   the 
variations  may  l^e  great.     These  depend,  first,  on  the  stage  of  the 
lesion;  secondly,  on   the  qualitative  features,  degenerative    or 
vascular  changes  predominating.     In  the  early  stages  the  evi- 
dences of  inflammatory  hypersemia  are  much  more  prominent 
than  later,  when  degenerative  and  particularly  exudative  changes, 
by  mechanical  compression,  aggregation  of  necrotic  material, 
and  by  the  general  oedematous  imbibition  of  the  parts,  change 
the  picture  from  red  to  gray  or  yellowish  pale,  and  make  the 
markings  gradually  indistinct,  and  cause  finally  entire  oblitera- 
tion. 


V 


/ 


X" 


J 


\ 

\ 


Fig.  7.— Nepliritis  degenerativa  exudativa  hsemorrhagica,  from  case  of  endocarditis 
septica.  A  large,  bulging,  uniformly  swollen  kidney.  All  normal  markings  lost.  Demar- 
cation between  medulla  and  cortex  obliterated.  Smaller  and  larger  hemorrhages  unevenly 
but  uniformly  distributed  over  the  whole  kickiey  cortex.  Interpolated  are  structureless 
yellowish-white  streaks  and  patches  wliich  correspond  to  exudative  and  degenerative 
(fatty)  areas.     The  reflected  capsule  oedematous,  vessels  injected,     'height,  300  gms. 


i)i';(;iv\i';ir\'ri\i';  and   i:.\ri)ATn'K   FKA'j'riuvs  ok  xioi'iiin'ris  69 


».»*^ 


■>•  -c 


Fig.  S.^Marked  cloudy  swelling  and  serous  imbibition  of  glomerular  capillaries,  lead- 
ing to  fusion  and  hyaline  swelling  of  the  lobules;  some  increase  in  number  and  size  of  endo- 
th(>lial  nuclei.  Serous  exudate  into  capsular  space,  leading  to  chlatation  and  to  hyaline 
swelling  of  the  capsular  epithelium,  which  is  gradually  lifted  off  the  basement  membrane 
and  pushed  toward  tlie  tuft.     Few  leukocytes  in  the  capsular  space.      X  260. 


Fig.    9. — Tuft    of   glomerulus    with   distinct  .separation   into  lol)ulcs;  intracapsular  exuda- 
tion more  marked.      X  2t)(). 


Fifi.  10. — \'an()us  glomerular,  periglomerular,  tubular,  and  peril  iilmlar  cluinKcs  in 
nephritis  exudativa  et  degenerativa,  partly  represented  in  Figs.  S  and  i).  In  addition, 
glomeruli  with  marked  intra-  and  pericapsular  e.xuflate,  with  necro.sis  of  one  ghjmerulus; 
anotlier  hyaline.  Patehy  cellular  exudate  in  periglomerular  and  intertuhular  tissue. 
Tubules  in  various  forms  of  parenchymatous  degeneration  and  necrosis.  In  tlie  uf)per 
part  of  the  picture  tubules  may  be  seen  to  contain  leukocytes.      X  125. 


1';^ 

m^^ 


Fig.  11. — In  the  upper  part  of  the  Held  a  glomerulus  shows  separation  into  distinct 
lobules  by  fusion  of  capillary  loops,  with  localized  attachment  to  capsule.  A  glomerulus 
below  this  shows  compression  by  exudate  and  hyaline  transformation  of  t  he  tuft.  Thicken- 
ing of  connective  tissue.     Cystic  dilatation  of  tubule  in  lower  part  of  field.     X  175. 

71 


DEGENERATIVE    AND    EXUDATIVE    FEATURES    OF    NEPHRITIS  73 


Fig.  12. — Fusion  of  glomerular  tuft  by  compression  of  exudate,  wliicli  leads  to  its  ne- 
crosis, and  also  dilates  the  capsule.  Below  it,  hyaline  (colloid)  cast  in  a  tubule.  Peri- 
glomerular  and  peritubular  cellular  infiltration.      X  260. 


Fig.  13. — Richly  cellular  (leukocytic)  exudate  into  glomerular  capsule,  with  disintegra- 
tion of  the  glomerulus.  Similar  exudation  in  surroimding  tissue  and  into  the  tubules, 
which  show  parenchjanatous  swelling.      X  210. 


DEGENERATIVK    AND    EXIDATIVE    FEATURES    OF    NEPHRITIS    ^r^ 


Fig.  14. — Typical  capsular  epithelial  proliferation  in  glomeruli,  becoming  gradually 
flattened  and  fil^rillar,  with  marked  fu.sion  of  capillaries,  leacUng  to  separation  of  glomerular 
lobules  and  final  disintegration.      X  185. 


DEGENERATIVE    AM)    EXCDATnE    FEATIHES    OF    NKI'HinTIS    // 


t 

r  » 


Fig.  15. — ^larked  purulent  infiltration  and  staphylococcal  emboli  in  the  glomerular 
loops,  which  ha^  extended  to  the  periglomerular  ti.ssue,  leading  to  necrosis  of  the  whole 
glomerulus.     The  surrounding  tubules  show  typical  parenchymatous  degeneration.     X  loO. 


•^Tfli 


*s»* 


Fig.  16. — Complete  piu-ulent  necrosis  of  glomeruli.     Capsular  space  and  tubules  relatively 

free.      X  200. 


degem:hati\  i:  and  fixidative  features  of  nephritis  79 


Fig.  16r/. — Topographical  picture  of  nephritis  exudativa  degenerativa  ha^morrhagica. 
In  the  upper  part  of  field  several  glomeruli  in  state  of  necrosis.  Cellular  infiltration  of 
interstitial  tissue.  Parenchymatous  degeneration  and  necro.sis  of  epithelial  cells  of  con- 
voluted tubules,  with  marked  hemorrhagic  exudate  into  them;    one  hyaUne  cast.      X  162 


Fig.  17. — Hemorrhagic  necrosis  of  a  glomerulus.     Necrotic  inflammatory  cells  surround  the 
glomerulus.     Hemorrhagic  exudate  into  tubules.      X  125. 


DEGENEKATINK    AM)    KX  IDATn'K    FKATTHKS    OF    NEPHRITIS  81 


i0-  ^    6 


JH 


Fig.  IS. — IiifUunnmtory  cxudiition,  fusion,  and  nccro.'^is  of  glomerular  tuft,  with  a'dematous 

swf'lling  of  capsular  epitliolium. 


i)K(ii;\KK.vri\  !■;  ami   i:\i  daj  i\  k   ika'I'i  I'.ks  ok  NKi'Hunis  83 


.»», 


© 


-      ^'/ 


9 


^ 


® 


4., 


/ 


Fig.  19. — Iloniorrhagic  fu-sion  and  nec-rosis  of  tuft.     The  surface  still  shows  few  drop.sical, 
swollen,  endothelial  or  epithelial  eells.     Edematous  swelling  of  capsular  epithehum. 


DEGENERATIVE    AND    EXri)ATI\I-:    FEATl'HES    OF    NEPHRITIS  85 

111  certain  cuses  heinorrlia<;es  occur  early  and  persistently, 
and  therefore  j^ive  to  the  whole  lesion  a  characteristic  appearance. 
For  the  sake  of  study,  wo  nia\-  (li\i(lc  tlie  manifold  microscopic 
processes  under  the  foUowinu  headint^s:  chancres  in  the  <!;lomeruli, 
chanjijes  in  the  tubular  substances,  chan^iies  in  the  intertulnilar 
substance. 

First,  the  chan«2;es  in  the  <>;lomeruli  have  been  well  studied 
and  are  of  the  <!;reatest  importance,  for,  as  we  will  see  later,  the 
ultimate  fate  of  the  kidney  depends  lar<>;ely  upon  them. 

The  first  chan*;es  in  the  glomeruli  are  de<!;enerative  in  char- 
acter and  affect  the  endothelium  of  the  capillaries  and  the  lininii; 
epithelium  of  tlie  tuft.  Coincident  is  inflammatorv^  hypersemia 
of  the  capillaries,  rapidly  followed  by  serous  imbibition  of  all  the 
structures  of  the  tuft.  In  severe  cases  all  of  these  are  well 
accentuated  from  the  start.  In  milder  cases,  von  Kahlden'"^'^ 
found  degenerative  features  the  very  first  phenomenon,  con- 
sisting mainly  of  fatty  degeneration  of  the  capsular  epithelium 
and  capillary  endothelium.  Even  in  these  milder  cases,  how- 
ever, inflammators^  oedema  into  the  tuft  and  into  the  space  be- 
tween it  and  the  capsule  follows  so  rapidly  that  it  cannot  well  be 
separated  from  the  degenerative  changes.  As  the  result  of  Ijoth 
of  these — degeneration  and  serous  exudate — the  capsular  epi- 
thelium is  lifted  off  the  basement  membrane  and  pushed  forward, 
the  epithelial  cells  of  the  tuft  loosen  and  desquamate,  hyaline 
swelling,  leading  to  thickening  and  turbidity  of  the  capillary 
walls,  occurs.  As  a  result  of  this,  fusion  of  the  lobules  follows 
with  the  characteristic  inflammatoiy  accumulation  of  leu- 
kocytes, and  their  emigration  into  the  tuft  and  capsule. 
The  appearance  of  free  red  cells  is  frequent.  The  exudate  lies 
partly  in  and  l)etween  the  convoluted  loops  and  lobules  of  the 
capillaries,  but  later  fills  the  capsule,  gradually  compressing  the 
convoluted  tuft  toward  a  peripheral  portion  of  the  capsule.     As 


86  bright's  disease 

a  consequence,  the  tuft,  thus  affected,  appears  primarily  large^ 
phimp,  pale,  filling  the  capsule  completely ;  but  later  the  capsule 
distends,  as  the  result  of  pressure  from  coagulated  exuded  masses 
and  cell  detritus,  and  leaves  the  capillaries  retracted  and  less 
conspicuous  (Figs.  8  to  12). 

]\Iuch  discussion  has  arisen  over  the  question  as  to  whether 
here  proliferation  of  the  epithelium  lining  the  tuft  occurs.  On 
account  of  the  complicated  pictures  in  the  tuft,  it  offers  particu- 
lar difficulty. 

I  do  not  share  the  view  that  this  takes  place  to  any  extent. 
Evidently,  the  initial  degenerative  changes  and  the  other  inflam- 
matory' conditions  make  this  impossible.  The  bulk  of  the  nuclear 
increase  within  the  tuft  appears  to  me  of  leukocytic  and  en- 
dothelial derivation  (Fig.  13).  On  the  other  hand,  proliferation 
of  the  epithelium  of  the  capsule  is  a  frequent,  rather  constant 
phenomenon.  It  is  seen  particularly  beautifully  in  scarlet  fever, 
and  sometimes  in  the  other  exanthemata,  severe  septic  condi- 
tions, also  in  SA'philis.  Whether  it  is  a  very  early  phenomenon 
is  doubtful.  Von  Kahlden  was  never  al^le  to  observe  it  in 
very  recent  cases.  It  is  certain  that  it  occurs  only  in  well 
established  nephrites.  One  can  observe  that  gradually  rows  of 
large  epithelial  or  epithelioid  cells,  following  the  inner  circular 
wall  of  the  capsule,  concentrically  advance  from  the  periphery 
toward  the  lumen.  This  proliferation  usually  commences  in 
those  glomeruli  which  have  become  widely  stretched  and  dilated 
by  free  exudate,  and  in  which  the  tuft  has  been  pushed  toward 
one  pole  (Fig.  14 j. 

r>om  the  opposite  direction,  this  epithelium  advances  into 
the  capsule,  inclosing  the  exuded  masses  within  it,  and  gradually 
assumes  a  characteristic  prominent  crescent  shape,  which  the 
German  pathologists  have  long  described  under  the  name  of 
"Halbmond"    (crescent)   pictures.     In  some  cases  it  becomes 


DEGENEKAT1\  ]•:    AM)    KXCDATIVK    Fi:ATrHP:s    OF    NEPHRITIS  87 


I 


^'.K  I 


3       # 


m: 


%»  •o  - 


Fig.  20. — Complete  granular  neorosis  of  glomerular  tuft,  surrounded  by  coagulated  serous 
exudate.     Few  swollen  epithelial  or  endothelial  cells  still  visible.      X  400. 


Fig.  21.— Destructive  parenchymatous  degeneration  of  tubular  epithelium.     Fusion  of 
granular  cellular  detritus  into  casts  within  dilated  tubules.      X  530. 


DEGENERATIVi:    AND    KXLJX\TIVE    FEATURES    OF    NEPHRITIS  89 


Fig.  22. — Higli  magnification  of  a  tubule,  \\-itli  granular  cytoplasmic  disintegration  and 

nuclear  loss. 


DKCKXKKA'riN  K    AM)    KX  T  DATI  \  K    FKATIKKS    OK    X  liJ'l  I  Kl'1'1  S   91 


Fig.  23. — Granular  cellular  ma.ssc.s,  loukocytos,  and  epithelial  ccll.s  in  tubule.s,  with 
extensive  necrosis  of  these  desquamated  cells,  inflaniniatory  engorp;ement,  and  hemorrhages 
of  intertuhular  ti.s.sue.      X  225. 


Fig.  24. — One  tubule  with  leukocytic  exudate,  another  with  epithelial  necrotic  masses,  two 
others  with  hyahnc  formation  in  tubules. 


DEGENERATIVE    AND    EXl'DATIVE    FEATURES    OF    NEPHRITIS  93 

excessive,  replaces  I  lie  whole  of  the  tuft,  and  un(ler«;oes  hyaline 
de<»:eneration.  This  epithelial  proliferation  appears  to  be  an 
inflammatory  phenomenon,  excited  here,  as  in  the  tubules,  by 
the  accumulation  of  necrotic  and  exuded  masses,  and  fulfils 
primarily  phaiiocytic-clearinti;  duty,  inau<i;uratin<>;  fibrous  and 
hyaline  replacement.     These  we  will  consider  later. 

Of  rarer  occurrence  are  the  formation  of  inflammatory 
hyaline  thrombi  in  the  capillaries,  described  by  Friedlander;  and 
Ribbert  observed  flatteninij;  of  the  thickened  linin<i;  epithelium, 
thereb}'  adding  to  a  compression  and  impermeability  of  the 
vessels  already  established  by  exudate  and  desquamated  en- 
dothelial cells.  Diapedesis  of  red  blood-cells  may  become  very 
marked,  with  severe  hemorrhages,  complicating  exudation  into 
the  tuft  or  capsule.  In  these,  rapid  necrosis  is  the  termination. 
When  the  exudate  becomes  purulent,  the  glomerulus  meets  the 
same  fate  (Figs.  15  to  20). 

Secondly,  as  regards  changes  in  the  tubules.  These  are  un- 
evenly distributed,  usually  more  intense  in  the  first  convoluted 
portion,  and  relatively  less  in  the  limbs  of  Henle  and  the  collecting 
tubules.  Senator^'  has  pointed  out  that  this  is  probably  the  re- 
sult of  the  greater  concentration  of  the  blood-current,  after  leav- 
ing the  glomerulus,  which  necessarily  exposes  the  epithelium  of 
the  convoluted  tubules  to  direct  and  greater  injury.  On  the 
other  hand,  the  experimental  investigations  of  Lyon^"  have  dem- 
onstrated that  in  certain  acute  intoxications  the  ascending  limb 
of  Henle  suffers  most  severely.  They  are  the  least  resistant  parts, 
and  show  disintegrative  and  necrotic  changes  more  commonly 
than  elsewhere.  The  cells,  in  thus  affected  parts,  show  intense 
parenchymatous  degeneration,  leading  to  fatty  degeneration  and 
necrosis.  Unlike  simple  nephritis,  the  tendency  is  here  to  de- 
struction and  loss  of  cells.  Swelling  and  turl^idity,  with  loss  of 
cellular  outline,  are  here  marked  from  the  beginning,  cell  masses 


94  bright's  disease 

fuse,  the  protoplasm  disintegrates  entirely,  and  fatty  substances 
tend  to  appear  in  the  form  of  fine  droplets ;  vacuoles  appear ;  the 
lariie  granules  of  the  cell,  l^y  confluence,  form  necrotic  masses, 
and  after  ])reaking  of  the  cell  membrane,  the  detritus  is  dis- 
charged into  the  lumen  of  the  tubules  (Figs.  21  to  24).  In 
severe  cases  the  lining  membrane  may  be  completely  desqua- 
mated ( Fig.  28 ) .  It  is  interesting  to  note,  and  was  first  pointed  out 
by  Ribbert,  that  the  appearance  of  fatty  substances  commences 
early  and  primarily  in  the  cells  of  the  loops  of  Henle,  and  if  we 
look  at  such  a  specimen,  one  cannot  help  being  astonished  at  this 
apparent  selective  location.  Later,  however,  all  the  cells  under- 
go the  same  fate.  Changes  in  the  nuclei  appear  later,  l^ut  are 
here  of  equal  severity,  leading  to  their  entire  loss.  They  are 
destroyed  either  by  rapid  chromatolysis,  with  some  persistence 
of  the  achromatic  substance,  or  the  chromatin  becomes  clumped, 
solid,  and  homogeneous,  so  that  the  original  structure  of  the 
nucleus  is  entirely  lost.  This  condition  is  known  as  pyknosis, 
and  eventually  results  in  breaking  up  into  smaller  chromatic 
masses  and  eventual  loss.  Finally,  nuclei  may  disappear  by  a 
primar}^  peripheral  displacement  of  the  normal  chromatin  masses 
in  the  nucleus,  leaving  its  body  pale.  These  chromatin  masses 
are  later  discharged  into  the  protoplasm  of  the  cell,  where  they 
gradually  disappear. 

Proliferation  of  the  epithelium  is  here  a  characteristic  and 
important  phenomenon.  It  is  excessive,  and  goes  hand  in  hand 
with  the  necrosis  of  the  epithelium  and  the  accumulation  of  in- 
flammatory detritus. 

For  this  reason  it  appears  usually  more  prominent  in  the 
lower  portion  of  the  tubules,  where  much  of  the  debris,  on  its 
removal,  stagnates ;  less  so  in  the  upper  parts,  but  may  assume 
there  as  great  dimensions,  if  the  necrosis  of  the  cells  and  the 
accumulation  of  inflammatory  detritus  assume  any  proportion 


dege.\i:kati\k  and  kxidviine  featirks  of  xephritis  95 


-Coinplcto  (losqiuinuilion  of  opithclium  of  tubules,  vdth  granular  contents  in  lumen 
of  tuhules.      X  400. 


Fig.  2G. — Marked  dilatation  and  distention  of  tubules.      X  12.5. 


DEGENERATIVE    AM)    K\  T  DA'J'I  \'J0    FEATIUIOS    OF    NEPHRITIS  97 


Fig.i_27. — Cast  formation:  Desquamation  and  proliferation  of  epithclivuii;  intertubular  en- 
gorgement.    Some  of  the  epithelium  pigmented.      X  400. 


Fig.  2S. — Hyaline  and  more  .solid  eolloid  casts  in  tubules.   Those  containing  the  casts  with 
peculiar  low  epithelial  cells  and  considerable  dilatation.      X  250. 


I)i:(il':.\KHATI\'K    AM)    KX  T  I)  ATI  \'K    FKATTRKS    OF    X  Kl'H  RITIS   99 

(Fi<»;s.  23  iind  124).  'I'liLs  iiiiportaiil  fact  appears  plain  from  tlic 
observations  of  Lyon,  Heine ke,  and  my  own.  The  cells  thus  de- 
rived from  the  linin»;  epithelium  of  the  tubules  differ  entirely  from 
the  normal  in  appearance  and  function.  In  the  lower  portion  of 
the  tubule  they  are  generally  small,  cuboidal  in  nature,  growing 
diffusely  within  the  tubules;  in  the  convoluted  parts  they  are 
much  larger,  frequently  forming  multinuclear  giant-cells  by 
fusion  or  overgrowth.  As  I  said  before,  their  function  must  be 
brought  into  relation  to  the  inflammatory  defenses  of  the  tissue. 
This  is  indicated,  not  only  by  their  distinct  morphology  and 
abundance  of  production,  but  also  by  the  phagocytic  power 
of  these  cells.  Regeneration  of  typical  permanent  epithelium 
does  not  occur  until  all  inflammatory^  irritants  and  products  have 
thus  been  removed,  but  then  with  great  activity.  The  process 
here  outlined  cannot  but  arouse  one's  great  interest  and  astonish- 
ment from  a  general  pathological  standpoint.  Consider  for  a 
moment  that  highly  differentiated  epithelial  cells,  under  the 
necessity  of  foreign  invasion,  so  to  speak,  throw  aside  their 
higher  attributes,  and  produce  an  offspring  which,  not  only 
morphologically,  l)ut  also  functionally,  is  distinct.  This  pro- 
duction is  continued,  as  necessity  requires,  over  and  over  again, 
until  after  a  time  the  cells  either  succumb  or  have  succeeded  in 
removing  the  cause  of  their  distress.  Then,  as  a  more  wonderful 
phenomenon,  they  are  able  to  reproduce  their  own  original  kind; 
return,  in  other  words,  to  their  former  morphological  and  func- 
tional differentiation.  In  this  process  are  concealed  from  us 
some  of  the  most  important  and  fundamental  biological  laws. 
If  we  ^^ne^e  able  to  follow  it,  we  would  know  w^hat  determines 
proliferation  of  cells,  what  determines  the  functional  differentia- 
tion, and  how  some  properties  may  remain  potential,  to  re- 
develop under  favorable  conditions.  It  would  be  the  greatest 
step  toward  the  solution  of  tumor  growth.     I  will  refrain,  how- 


KM)  BRIGHT  S   DISEASE 

ever,  from  uoiiiii"  into  theoretical  discussions  here  and  return  to 
facts. 

The  himen  of  the  tubules  contains  more  than  this  material; 
leukocytes,  red  cells,  coa<iulated  albuminous  exudate  enter 
partly  through  their  own  injured  walls,  and  to  some  extent  are 
washed  down  from  the  glomeruli.  As  a  consequence,  the  tubules 
enlarge,  so  that  their  lumen  is  frequently  double  the  size  of  a 
normal  one  (Fig.  26).  Gradually  the  contents  are  moved  to- 
ward the  pelvis  of  the  kidney,  and  finally  are  washed  out  with 
the  urine,  or  pressed  and  fused  into  casts. 

To  the  latter  we  must  now  pay  attention.  Casts  are  either 
cellular  or  they  are  homogeneous,  pale,  transparent  hyaline,  or, 
if  thicker  and  more  solid  in  appearance,  waxy;  finally  granular. 
Xot  infrequently  they  may  be  mixed  by  the  adhesion  of  cells  to 
a  hyaline  or  waxy  ground  matrix  (Figs.  24,  27,  and  28). 

The  origin  of  the  cellular  casts — epithelial,  leukocytic,  blood- 
casts,  and  the  granular  varieties — can  be  easily  traced  to  fusion 
of  these  substances  within  one  or  another  part  of  the  tubules. 
\er\'  difficult  and  disputed,  however,  has  been  the  origin  of  the 
hyaline  and  waxy  types.  A  number  of  investigators  believe 
that  they  originate  from  fusion  of  desquamated  epithelial  pro- 
toplasmic remnants.  Others,  however,  believe  that  they  are 
the  product  of  an  allnmiinous  exudate  into  the  tubules.  The 
formation  from  fibrin  has  also  been  advocated,  and  finally  it  is 
held  that  they  are  the  product  of  a  specific  secretion  of  hyaline 
globules  of  the  epithelial  cells.  The  literature  on  the  formation 
of  casts  is  very  extensive,  so  that  it  will  l)e  impossible  to  even 
}>riefly  review  all  of  it. 

Doubtless  you  recall  that  it  was  the  great  anatomist  Henle  ^^ 
who  first  discovered  this  relationship  and  importance  in  connection 
with  the  inflammations  of  the  kidney.  He  interpreted  them  as 
fibrin  coagula.     Rovida'^'^  later  thoroughly  analyzed  them  chemi- 


DEGENERATIVE  AND   KXIDATI  \'l';   KKATlltES  OF   .\  Kl'H  HI'J'IS    101 

(•ally  and  dcnionst rated  thoni  as  albuininoid  bodies.  Since  then 
ven'  numerous  anatomical  and  experimental  investi«i;ations  have 
endeavored  to  demonstrate  their  exact  derivation  and  chemical 
constitution.  Physically  these  hyaline  casts  are  usuall\  under 
1  mm.  loni;-,  and  the  thickness  is  between  0.01  and  O.Oo  mm. 
Their  shape  necessarily'  \'aries  accordin<>;  to  the  tul)es  they  come 
from  ;  and  on  their  downward  way  they  are  frequently  broken  or 
bent.  In  the  kidneys  they  may  be  found  in  all  parts  of  the  tu- 
bules, but  with  particular  frequency  in  the  loops,  undoubtedly 
on  account  of  the  mechanical  difficulty  of  propulsion  there. 
A  relationship  between  albuminuria  and  cast  formation  does  not 
seem  to  exist ;  and  one  may  be  abundant  without  the  other.  This 
fact,  as  well  as  their  apparent  different  chemical  constitution,  has 
been  particularly  emphasized  l:)y  those  who  do  not  recognize  their 
derivation  from  exuded  serum-albumin.  On  the  other  hand, 
Weissgerber  and  Perls  ^°  and  Ribbert^^  are  of  the  opinion  that 
these  casts  represent  a  hyaline  transformation  of  exuded  albumin. 
It  would  be  necessary  to  assume  for  this  a  ferment  action.  Rib- 
bert  denies  a  derivation  from  desquamated  and  degenerated  cells. 
Orth"*-  also  recognizes  transudate  casts,  and  in  support  draws 
attention  to  the  occurrence  of  hyaline  masses  between  the  tunica 
propria  and  uninjured  epithelium  in  some  kidneys.  But  he 
further  believes  that  the  previously  mentioned  h3'aline  and 
colloid  globules,  which  appear  in  the  cells  during  the  process  of 
parenchymatous  degeneration,  may  be  discharged,  and  fuse, 
with  the  formation  of  casts.  He  calls  these  '*  secretion  casts." 
Similar  are  the  views  of  Landsteiner,^'^  who  holds  that  hyaline 
bodies  develop  in  the  epithelial  cells  as  a  result  of  pathological 
stimuli.     They  are  discharged  and  fuse  to  casts. 

Ribbert,  on  the  other  hand,  claims  that  such  hyaline  bodies 
may  be  observed  in  healthy  kidneys,  and  that  any  relation  to  the 
formation  of  casts  does  not  exist.    Pfister^^  observed  the  occur- 


102  bright's  disease 

rence  of  granules  within  the  degenerating  cells,  which  responded 
to  the  fibrin  stain  of  Weigert,  and  also  in  other  staining  qualities 
resembled  casts.  Similar  had  been  the  views  of  Henle,  and  later 
Klebs,  Israel,  and  Ernst/'^  who  regarded  them  as  fibrin,  particu- 
larh'  as  the}'  answered  to  Weigert's  fibrin  stain.  This  has  been 
contradicted  by  Lubarsch,^*^  who  holds  that  other  substances  give 
similar  reactions,  and  that  the  diagnosis  of  fibrin  must  be  made 
on  morphological  as  well  as  tinctorial  grounds.  Much  confusion 
has  arisen  over  the  nature  and  significance  of  waicy  casts.  They 
have  been  regarded  by  some  as  amjdoid,  on  account  of  certain 
reactions,  but  they  occur  in  all  forms  of  nephritis,  are  of  variable 
reaction,  and,  in  all  probability,  are  not  amyloid. 

Lyon"^'  regards  casts  as  either  a  coagulation  of  an  intratubular 
transudate  or,  in  the  majority  of  cases,  arising  by  granular 
disintegration  or  colloid  transformation  of  secreting  cells. 

It  appears  that  all  casts  are  probabl}^  not  of  definite  uniform 
character  and  derivation.  This  is  made  likely,  not  only  by  the 
multitude  of  observations  of  their  derivation,  but  more  so  by 
their  extremely  variable  morphology  and  chemical  character, 
as  is  particularly  well  shown  in  their  different  staining  affinities. 
Sometimes  they  stain  faintly  with  eosin,  sometimes  rather 
deeply;  occasionally  they  seem  to  have  some  affinity  for  basic 
stains.  With  iodin  the}^  stain  from  dark  l^rown  through  all 
shades  to  yellow;  with  methyl- violet,  blue,  but  also  violet  or 
pinkish.  On  the  other  hand,  waxy  casts  never  give  the  iodin- 
sulphuric-acid  reaction  for  amyloid,  and  are  better  termed  colloid 
casts,  to  avoid  confusion. 

I  therefore  believe  that  the  origin  of  these  casts  depends 
upon  several  factors,  and  is  inconstant.  Epithelial  cells,  by 
granular  disintegration  and  subsequent  hyaline  transformation, 
can  apparently  furnish  material  for  their  formation,  and  this 
process  can  be  directly  demonstrated  in  all  stages.     That   a 


DEGENERATIVK  AND  EXT  DATIVE  FEATURES  OF  NEPHRITIS    103 

colloid  secretion  is  furnished  hy  the  cpitlicliiiin  is  not  {H'obable, 
l)u( ,  more  likely,  that  a  colloid  de^'eneration  oi-  1  ransformation 
of  tli(>  cells — as  Lyon  expresses  it — contributes  toward  them. 
Finall}',  it  appears  thai  both  of  these  substances  may  fuse  with 
inflammatory  albuminous  exudate.  We  can  recognize,  there- 
fore, these  three  factors  that  enter  into  cast  origin,  and  as  one 
or  the  other  predominates  or  may  be  absent,  the  character  of 
the  cast  varies  physically  and  chemically.  These  views  are 
further  supported  by  the  observations  of  Litten,"*^  who  demon- 
strated not  only  the  participation  of  coagulated  epithelial 
matter,  but  also  the  addition  of  transuded  serum-albumin;  and 
Langhans,*^  who  saw  not  only  epithelium,  Ijut  also  changed 
leukocytes  and  red  blood-cells  entering  into  their  combination. 
That  in  the  presence  of  much  disintegrated  cell  material,  fer- 
ment action  may  play  a  role'^^  to  further  change  the  constitu- 
tion of  these  substances,  and  cause  coagulation,  seems  likely. 
Ribbert  contends  that  the  acid  reaction  of  the  urine  may  be  a 
factor  in  the  coagulation  of  albuminous  matter  to  casts. 

A  few  words  about  cylindroids.  These,  as  you  know^,  are 
pale,  long,  tortuous,  narrow,  usually  distinctly  striated  bands  or 
ribbon-like  formations.  One  end  is  usually  rounded,  while  the 
other  extremity  frequently  presents  a  torn,  fibrillated  appearance. 
Some  hold  them  closely  allied  to  hyaline  casts;  others,  however, 
— and  I  share  the  view, — believe  that  they  are  mucoid  threads, 
which  owe  their  origin  either  to  prostatic  secretion  or  secre- 
tions from  Cowper's  and  Littre's  glands.  They  occur,  some- 
times in  otherwise  normal  urine,  in  great  abundance,  but  particu- 
larly with  other  mucoid  and  slimy  matter.  On  the  other  hand, 
they  do  not  seem  to  have  any  relation  to  the  inflammations  of  the 
kidney,  and  I  have  never  seen  anything  in  kidney  sections 
which  resembled  them.  This  makes  it  probable  that  they  owe 
their  origin  to  other  parts  of  the  genito-urinary  tract. 


104  bright's  disease 

Thirdly,  the  changes  in  the  intertubular  interstitial  tissue. 
This  is  not  only  the  supporting  connective-tissue  frame  of  the 
parenchyma,  but  the  carrier  of  blood-vessels,  lymphatics,  and  the 
nerves.  The  changes  occurring  in  it  are  partly  dependent  on  a 
primary  involvement  of  these  structures,  but  largely  also  upon 
the  modifying  influence  which  the  involvement  of  one  of  these 
parts  exerts  upon  the  other.  On  the  other  hand,  it  is  influenced 
in  turn  b}'  the  pathological  relations  of  the  neighboring  parenchy- 
matous structures.  To  make  this  clear:  The  changes  in  the 
blood-vessels  bring  about,  of  necessity,  alterations  in  the  lym- 
phatics, which  again  reflect  upon  the  vascular  apparatus 
and  the  surrounding  connective  tissue.  But,  further,  while 
these  changes  affect  the  tubules,  their  disturbances,  by  necessary 
interchange,  cause  subsequent  pathological  alterations  in  the  in- 
terstitial tissue.  It  will  give  you  an  idea  how  intimately  all  these 
various  structures  are  related,  and  that  much  of  the  complex 
picture  of  the  disease  is  not  necessarily  the  result  of  direct  injury 
or  invasion,  but  a  subsequent  development,  the  result  of  disturbed 
anatomical  relations.  This  accounts,  in  no  small  degree,  for  the 
great  individual  variations  which  we  daily  meet  in  all  diseases. 

The  first  change  which  this  interstitial  tissue  shows  is  inflam- 
matory hypersemia.  This  leads  to  compression  of  the  rest  of 
the  interstitial  substance,  lymphatics,  and  tubules.  Resorption 
must,  therefore,  be  interfered  with  from  the  beginning.  Closely 
following  is  the  development  of  inflammatory  oedema.  This 
must  be  attributed  to  slowing  of  the  blood-current,  increased 
permeability  of  the  vessel-walls,  and  lack  of  resorption  on  the 
part  of  the  lymphatics.  This  inflammatory  oedema  leads  to 
imbibition  of  the  connective-tissue  structures  and,  as  we  saw  be- 
fore, the  epithelium  of  the  surrounding  tubules.  The  connective- 
tissue  fibers  separate,  become  stretched,  glassy,  pale,  inflexible; 
and  stagnation  of  blood-and  lymph-streams  follows.   Then  occurs, 


DEGENERATIVE  AND  EXUDATIVE  FEATURES  OF  NEPHRITIS    105 


Fig.  29. — Periglomerular   interstitial  cell  infiltration  around  a   hyaline  glomerulus, 
adjoining  tubules  much  dilated.      X  240. 


The 


dec; km: RATI \H   \\\)   KXUDATIVE  FEATURES  OF  NEPHRITIS    107 

first  patch}',  but  l)ecoiiiin^'  streaky  and  fiiiall\'  diffuso,  a  cellular 
exudation,  around  <>lomeruli  and  l^etween  tubules  (Fi<!;.  29).  The 
emit»rated  cells  lodj^e  in  lymphatics  and  tissue  spaces,  producing 
a  lymphan<2;itis  and  perilymphan^^itis.  They  proo;ress  within 
these  preformed  channels,  but  also  get  into  the  tubules,  particu- 
larly attracted  by  necrotic  and  degenerating  portions.  The 
character  of  these  cells  varies  in  different  types  of  inflammations 
and  different  stages  of  the  process.  Councilman  has  shown  that, 
particularly  in  certain  of  the  acute  exanthemata,  the  whole 
exudate  may  consist  primarily  of  so-called  mononuclear  plasma 
cells  and  emigrating  tymphoc^^tes.  Later  in  the  process,  as  the 
parenchymatous  destruction  becomes  manifest,  polymorphonu- 
clear types  prevail. 

The  exudate  contains  most  always  some  red  blood-cells,  and 
sometimes  streaky  or  diffuse  hemorrhages  occur.  This  is 
noticeable  particularly  in  scarlet  fever  and  in  other  severe  septic 
infections  which  have  a  tendency  to  marked  injury  of  the  vessel- 
walls.  The  blood  is  discharged  into  the  tissue  spaces  and  tubules. 
In  these  more  severe  cases  fibrin  is  also  present.  Under  these 
circumstances  the  kidney  becomes  succulent,  softer,  and  an 
abundant  turbid  fluid  may  l^e  squeezed  out  on  section. 

However,  these  are  not  the  only  changes  which  are  promi- 
nent in  the  interstitial  tissue.  Connective-tissue  and  endothelial 
cells  undergo  cloudy  swelling  and  fatty  changes.  The  latter  may 
become  very  marked,  and  lead  to  accumulation  of  abundant  fat- 
drops  in  the  interstitial  tissue  and  within  tissue  and  lymphatic 
spaces.  Lohlein''-  regards  this  as  an  indication  of  resorption. 
The  fatty  substances  are  parth^  ordinaiy  fat,  partly  doubly 
refracting  myelin  substances,  and  partly  a  crystalline  protagon- 
like  body.  1  will  discuss  these  matters  in  detail  in  connection 
with  fatty  degenerative  nephritis.  It  remains  to  sketch  the 
functional  disturbances  thus  induced. 


108  bright's  disease 

The  severe  changes  in  the  giomeruh  and  tubules  necessarily 
lead  to  a  marked  diminution  in  the  amount  of  urine,  sometimes 
to  almost  an  anuria.  The  urine  thus  becomes  necessarily  high 
colored,  and  gradually,  as  exudate  and  cellular  detritus  appear  in 
it,  turbid,  and,  as  blood  appears,  smoky.  The  specific  gravity 
is  high,  and  this  in  spite  of  the  fact  that  the  normal  urine  constit- 
uents are  markedly  diminished.  This  is  not  only  due  to  the 
great  concentration  of  the  urine,  but  more  especially  to  the 
presence  of  large  amounts  of  serum-albumin,  with  nucleo- 
albumin,  the  former  being  derived  from  the  abundant  exudate 
and  free  blood,  the  latter  from  the  cellular  destruction.  Mor- 
phologically, such  a  urine  contains  all  varieties  of  cells  of  the 
exudate :  leukocytes,  free  blood-cells,  mononuclear  cells,  and 
a  large  number  of  desquamated  and  newly  formed  epithelial 
cells.  Necrotic  cell  masses  are  also  present.  Casts  are  very 
numerous — blood,  leukocytic,  epithelial,  granular,  fatty,  hya- 
line, and  waxy,  with  the  cellular  type  predominating.  Many 
of  the  blood-cells  undergo  haemolysis,  setting  the  pigment  free, 
which  adds  to  the  characteristic  smoky  color  of  the  urine. 

These  evidences  vary  necessarily  with  the  predominance  or 
absence  of  these  pathological  changes,  and  this  leads  me  to  say 
a  few  words  about  these  variations  and  their  probable  cause. 

No  doubt  you  appreciate  that  what  I  have  presented  to  you 
here  is  a  composite  picture,  subject  to  many  individual  modifica- 
tions. Out  of  these  we  can  recognize  two  larger  groups:  one 
in  which  the  process  is  related  more  particularly  and  energetically 
to  the  vascular  apparatus,  and  one  in  which  the  process  is  pre- 
dominatingly degenerative  and  proliferative  among  the  fixed 
cells  of  the  kidney.  As  one  or  the  other  predominates  and  in- 
fluences the  later  manifestations  of  the  disease,  we  can  recognize 
that  exudative  or  degenerative  and  proliferative  features  pre- 
dominate, and  therefore  give  to  the  whole  lesion  a  characteristic 


DEGENERATIVE  AND  EXUDATIVE  FEATURES  OF  NEPHRITIS    109 

stanij).  Tlic  cause  for  this  lies  iindoiihtcdly  not  only  in  the 
question  of  (luantitativc  irritation,  hut  in  the  peculiar  affinity 
whicii  certain  invasions  have  for  one  or  the  other  tissue.  It  has 
been  found  by  Baum<i;arten,  for  instance,  that  the  introchiction  of 
tubercle  bacilli  leads  mainly  to  the  formation  of  <!;ranulomatous 
tissue,  while  the  introduction  of  the  toxin  without  bacteria  is 
followed  mainly  by  exudative  processes.  The  same  fact  applies 
to  other  intoxications  and  poisons.  Snake  venoms,  for  instance, 
have  a  greater  destructive  and,  therefore,  reactive  effect 
on  the  vascular  apparatus.  In  scarlet  fever  this  has  long  been 
recognized.  On  the  other  hand,  certain  diseases  and  poisons 
exert  the  greatest  destructive  influence  on  the  fixed  cells,  and 
their  lesions,  and  results  therefrom,  are  more  evident  and 
dominating  in  such  cases. 

Certainly  it  would  be  a  mistake  to  endeavor  to  draw  lines  of 
mathematical  distinction  between  these  various  manifestations. 
In  the  end,  we  are  dealing  with  one  or  another  accentuation  of 
features  of  a  nephritis,  not  with  independent  distinct  diseases. 
It  is  only  for  the  purpose  of  study  that  we  can  divorce,  or  abstract 
them  from  the  others,  thus  lifting  them  above  concomitant, 
correlated,  and  dependent  changes. 


FOURTH  LECTURE  * 

The  Results  and  Terminations  of  Degenerative  and  Exu- 
dative Nephritis.     Productive    Changes    in    the 

Kidney 

Gentlemen: 

We  have  followed  the  nephritic  process  to  the  height  of  its 
development.  WTiat  are  its  terminations?  They  are  three: 
first,  fatal;  second,  attenuation,  with  certain  modifications  in 
the  inflammation,  which  allows  progress  in  a  less  brusque  manner, 
and  therefore  extends  over  a  prolonged  period  of  time;  third, 
latency,  with  constant  danger  of  exacerbation,  and  ultimate  fatal 
termination.  I  have  not  included  recovery  in  this  list,  because  I 
consider  it  extremely  doubtful  whether  actual  restitution  to 
integrity  ever  occurs  in  severe  nephritis,  and  whether  it  can  ever 
be  regarded  as  healed  or  cured,  in  the  sense  in  which  these  terms 
are  ordinarily  emploj^ed.  If  you  recall  for  a  moment  the  severe 
destructive  changes  which  we  observed  in  the  glomeruli,  and 
the  anatomical  arrangement  of  the  glomerulus,  you  will  probably 
agree  that  the  structure  has  not  only  been  permanently  injured 
and  destroyed,  but  that  regeneration  to  its  former  state  must  be 
out  of  question.  It  is  true  that  cells  may  regenerate  rapidly, 
jjut  this  requires  that  the  anatomical  arrangement  of  the  part 
has  not  been  lost ;  it  remains  confined  to  cells  within  established 
structures.  The  tuft  once  destroyed  in  a  glomerulus  cannot 
reproduce  a  new  one.  No  one  has  ever  seen  new  glomeruli  or 
tubules  form,  nor  even  a  new  tuft  within  an  old  glomerulus 
capsule.'  This  destruction  remains  a  permanent  loss,  and  the 
organism  must  help  itself  in  some  other  way.     Undoubted^, 

*  Delivered  on  February  11,  1909. 
110 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS  111 

mail}'  i;l()ni('ruli  liavc  not  hccn  injured  to  .such  extent  as  to  cause 
entire  obliteration  of  the  tuft.  Amelioration  of  the  inflammation 
will  make  possible  at  least  some  functional  activity — in  some  more 
than  in  others;  liowever,  the  pathological  chan<i;es  in  them  have 
at  least  permanently  affected  the  normal  structures,  and,  while 
not  completely  annihilating  them,  leave  them  in  an  injured 
state,  constantly  in  danger  of  inflammatory  exacerbations. 
This  is  particularly  unfortunate  and  dangerous,  inasmuch  as  they 
are  called  upon  to  increase  their  work  in  order  to  compensate 
those  which  hav^e  been  entirely  eliminated.  This  necessar}^ 
increased  functional  activity  and  irritation  make  them  more 
vulnerable  and  hasten  the  ultimate  fate  of  final  destruction.  In 
the  tubules,  as  we  will  learn  presently,  a  very  similar  state  of 
affairs  exists.  Indeed,  strong  evidence  has  gradually  accumulated 
which  points  to  the  fact  that  many  of  the  so-called  primary 
contracted  kidneys,  or,  better,  cases  of  productive  nephritis, 
are  really  of  the  so-called  secondar}^  type;  that  they  found  their 
original  start  in  a  degenerative  exudative  nephritis,  sometimes 
fifteen,  twenty-four,  or  twenty-eight  years  ago,  most  frequently 
during  the  course  of  a  scarlet  fever.  The  recovery  in  these  cases 
was  onlyapparent ;  the  disease  continued  slowly  but  progressively, 
in  a  manner  to  which  the  organism  adapted  itself,  and  therefore 
enjoyed  relative  health  for  j^ears,  until  the  disease  had  finally 
reached  a  stage  when,  as  out  of  a  clear  sky,  a  fatal  catastrophe 
occurred.  In  reality,  therefore,  of  verv^  long  duration.  Clinicians 
like  Heubner  and  Dixon  Mann  have  long  emphasized  such  cases. 
Only  recently  F.  Muller-  said:  "The  kidney  is  a  treacherous 
organ,  which  may  carry  latent  an  injur}^  for  decades,  to  finally 
cause  sufTering  and  death." 

Most  convincing  are  the  observations  of  Lohlein,^  because 
they  furnish  an  objective  anatomical  basis  for  these  ideas.  I 
have  already  touched  upon  them  in  the  first  lecture,  but  you  will 


112  bright's  disease 

recall  that  he  found  that  these  so-called  secondary  contracted 
kidneys  are  much  more  frequent  than  supposed,  and  may  be 
traced  to  previous  stages  of  degenerative  and  exudative  nephritis. 
He  also,  you  recall,  drew  attention  to  a  type  of  cases  which,  having 
passed  through  a  so-called  acute  attack,  enjoyed  relative  health, 
and  then  suddenly  died  with  all  the  symptoms  of  nephritis.  In 
them  he  found  typical  productive  glomerulonephritis  with 
marked  contraction  of  the  organ;  the  process  must  have  gone 
on  insidiously,  but  no  less  perniciously,  for  years.  Similar  are 
the  views  of  Aufrecht. 

My  own  observations  in  the  matter  fully  corroborate  these 
contentions,  and  I  am  of  the  opinion  that  at  least  the  majority 
of  cases  of  late  nephritis  have  been  ushered  in  by  previous 
degenerative  exudative  lesions,  which,  having  become  latent, 
have  been  disregarded  clinically  until  their  progress  has  led  to  a 
point  where  the  organism  is  unable  to  adapt  itself.  Then  it  pro- 
duces manifestations  which  appear  new  and  sudden,  but  might 
have  been  anticipated  long  ago.  Unquestionably,  this  has  much 
practical  bearing  in  the  matter  of  prognosis  and  in  the  matter  of 
treatment  also.  One  should  be  very  cautious  in  giving  an  opti- 
mistic ultimate  prognosis  in  any  degenerative  exudative  nephritis, 
and  no  doubt  many  more  cases  of  nephritis  could  be  benefited  by 
treatment  if  they  were  more  carefully  watched  for  a  long  time  after 
the  evidences  of  the  brusque  initial  lesions  had  subsided,  and 
later  at  intervals.  But  here,  as  in  other  diseases,  advice  is  not 
sought,  and  the  early  stages,  still  amenable  to  treatment,  are  dis- 
regarded by  the  patient,  and  unfortunately  also  by  the  physician. 
Both  usually  pay  no  attention  to  a  disease  until  it  becomes 
manifest  in  an  entire  upset  of  an  organism's  economy.  Phy- 
sicians are  not  always  at  fault  at  this.  Our  diagnostic  methods 
at  the  best  are  indelicate,  and  give  information  only  in  severe 
interferences.     But  it  seems  that  much  of  the  continued  careful 


DEGENERATIVE    AND    EXUDATI\K    .NEPHRITIS  113 

()b.ser\alioii  has  ]xissetl  out  of  medicine  in  a  hasty  progress. 
Perhaps  the  old  physician,  in  spite  of  his  lack  of  knowledge,  may 
liave  been  unconsciously  a  better  physician  in  many  instances. 
His  close,  constant,  and  friendly  association  with  patients,  whom 
he  frequently  saw  and  consulted  witli,  allowed  liim  perhaps  to 
form  much  earlier  and  l^etter  opinions  of  expression  of  disease 
than  we  are  now  able  to  attain  with  our  hasty,  purely  objective 
methods.  Much  used  to  enter  into  the  legitimate  practice  of 
medicine  which  now  has  passed  away  for  lack  of  time,  or  has 
been  consumed  by  the  charlatanism  of  schools,  and  exaggerated 
by  uneducated,  unrefined  followers.  Dilettantism  and  notoriety 
to-day  march  under  the  flag  of  l)road  scientific  knowledge  and 
business  methods.  People  forget  that  the  human  mind  can  only 
do  relatively  few  things  thoroughly  and  reliably,  and,  therefore, 
that  in  science  and  art,  unlike  business,  quantity  never  goes 
with  quality.  Nowhere  are  careful,  painstaking,  and  long- 
continued  observation  and  treatment  more  strongly  indicated 
and  of  greater  importance  to  the  patient  than  in  nephritis. 

We  shall  now  proceed  to  consider  in  detail  the  further  changes 
in  the  kidney,  commencing  with  the  time  we  reached  at  the 
end  of  the  last  lecture. 

After  the  processes  of  parenchymatous  destruction  and  exu- 
dation have  attained  the  height  to  which  we  traced  them,  there 
occurs,  provided  that  the  individual  does  not  die,  a  relative 
standstill.  By  this  do  not  misunderstand  that  things  halt 
entirely,  but  the  process  has  arrived  at  a  point  where  rapid 
progress  and  uniformity  of  degenerative  and  exudative  phenom- 
ena stop  and  evidences  of  regression  and  attenuation  become 
visible,  gradually  leading  to  new  pathological  processes,  which 
give  to  the  whole  a  greater  variety  of  pictures.  This  depends 
probably  upon  complex  qualitative  as  well  as  quantitative 
changes  within  the  kidney  and  the  irritant.     It  would  lead  me 


114  bright's  disease 

here  too  far  to  enter  into  a  detailed  discussion  of  this  question, 
but  I  will  only  indicate  to  you  that  this  must  be  attributed,  first, 
to  the  changes  which  the  inflammation  has  produced  in  the 
tissues  of  the  kidne}^  and  in  their  anatomical  arrangement.  Into 
this  naturally  enter  the  qualitative  changes  within  the  cells  and 
mechanical  factors  due  to  the  rearrangement  of  the  parts.  Second, 
owing  to  the  changes  in  the  irritant  brought  about  by  the  in- 
flammatory condition  of  the  organ,  much  of  it  has  been  directly 
destroyed,  or  at  least  altered.  Both  these  points  are  complex  and 
intricate,  and  involve  man}^  other  problems,  and  I  therefore  can- 
not fuUy  discuss  them  within  the  scope  of  these  lectures.  Suffice 
it,  therefore,  if  3^ou  appreciate  that  the  inflammatory  alterations 
in  the  structure  of  the  kidney  and  the  concomitant  changed  rela- 
tionship to  the  inflanunatory  irritant  have  drifted  to  a  point  where 
the  original  response  of  the  tissues  to  the  invasion  necessarily 
ceases  and  undergoes  decided  modifications.  These  modifica- 
tions in  the  inflammatory  process  are  expressed  in  two  main 
changes :  first,  lessened  exudation ;  and,  second,  fatty  degenera- 
tion and  infiltration  of  the  remaining  parts.  They  result  from 
obliteration  and  blocking  of  the  normal  paths  of  nutrition  and 
resorption.  Consequently  nutritive  disturbances  now  commence 
to  control  the  picture,  associated  by  degrees  with  inflammatory 
exacerbations  and  remissions,  and,  as  the  substance  wastes, 
more  or  less  extensive  productive  changes. 

We  shall  deal  with  these  changes  in  the  order  here  enumer- 
ated. First,  then,  the  nutritive  disturbances.  These  manifest 
themselves  in  various  degenerative  processes,  which  either  were 
originall}"  absent  or  less  prominent.  Colloid  and  hyaline  bodies 
appear  in  great  number  within  the  disintegrating  parench3^ma 
cells ;  autolytic  processes,  undoubtedl}^  due  to  ferment  formation 
from  broken-down  cells,  become  conspicuous;  but  the  fatty 
changes  are  apt  to  supersede  all  others  in  prominence.     They 


DEGENERATIX'E    AND    EXUDATIVE    NEPHRITIS  115 

soon  ^ive  to  the  whole  type  of  nephritis  a  cliaracteristic  appear- 
ance. As  the  result  of  these  various  de<!;enerations,  all  of  which 
go  along  with  swelling  of  cells,  the  kidney  as  a  whole  enlarges. 
This  is  further  (hie  to  the  flifhculties  in  resorption  and  nutrition 
of  the  parts,  to  capiHary  and  lymphatic  obliteration,  which 
allows  broken-down  material  to  collect  and  stagnate.  It  is  also 
added  to  by  the  presence  of  iiiflammator}'  oedema,  and  the 
occasional  exudative  exacerbations.  All  of  these  contribute  to 
a  gradual  but  ver\'  marked  increase  in  the  size  of  the  organ  and 
an  obliteration  of  its  normal  markings.  These  give  way  to  a 
more  uniform,  anaemic,  yellowish-pale  color,  interchanging  with 
areas  of  vascular  injection  where  the  process  is  exudative  or 
productive,  or  ^vhere,  clue  to  obliteration  of  old  normal  channels, 
compensator}'  dilatation  of  vascular  canals  has  occurred.  At  this 
point  of  the  process  the  capsule  still  strips  easily,  the  surface 
bulges  very  prominently,  as  so,  on  section,  does  the  cortex.  The 
normal  markings  appear  lost  or  much  distorted.  The  glomeruli 
are  pale  and  glistening,  the  medulla  dull  pale  yellow  in  color, 
and  the  line  of  demarcation  between  it  and  the  cortex  poorly 
accentuated.  In  short,  it  presents  the  kidney  now  spoken  of  as 
chronic  parenchymatous  nephritis,  or  large  white  kidney ;  better 
and  more  correctly,  as  I  termed  it  at  the  beginning  of  these 
lectures,  the  degenerative  fatty  nephritis.  Inasmuch  as  these 
fatty  substances  play  such  a  role,  we  must  have  a  clear  picture  in 
our  mind  what  they  are,  and  what  is  their  derivation  and 
significance.  Here  we  enter  another  ver\'  much  disputed  and 
much  fought  over  ground  of  general  pathology.  You  must, 
therefore,  be  content  with  a  short  summary-  of  the  situation. 

You  are  aware  that  Virchow^^  originalh'  distinguished  between 
two  types  of  fatty  changes:  degeneration  and  infiltration.  In 
the  latter  he  assumed  that  the  fat  was  brought  to  the  part,  while 
in  the  former  occurred  a  direct  transformation  of  the  protein 


116  bright's  disease 

portion  of  the  protoplasm  into  fat.  This  involved,  then,  an 
active  and  much  more  severe  permanent  destruction  of  the  pro- 
toplasm, while  infiltration  was  passive.  Support  of  this  idea 
came  in  the  celebrated  observations  of  von  Voit  and  Petten- 
kofer,^  later  followed  by  others,  particularly  Bauer  and  F.  Hof- 
man,  and  followed  by  the  critical  review  of  Pfliiger.^  The  latter 
demonstrated  that,  although  a  direct  transformation  of  protein 
into  fat  cannot  be  denied,  there  is  no  sufficient  proof  that  this 
actually  occurs.  If  at  all  possible,  it  seems  most  probable  by  a 
primar}'  splitting  off  of  carbon-poor  decomposition  products, 
with  a  following  synthesis. 

For  these  reasons,  and  particularly  on  account  of  gradually 
accumulating  experimental  evidence,  the  idea  of  fatty  degenera- 
tion became  gradually  replaced  by  that  of  fatty  infiltration.  It 
is  particularly  to  Rosenfeld"  that  we  owe  the  most  convincing 
testimon}^  in  its  favor.  He  determined  the  ether  extract  of 
normal  organs  and  compared  it  with  that  of  fatty  ones.  He  and 
Rumpf  ^  observed  a  variable  but  decided  increase  from  25  per 
cent,  to  30,  40,  60,  and,  in  phosphorus-poisoning,  even  75  per 
cent.  These  large  percentages  appeared  to  Rosenfeld  as  only 
ascribable  to  infiltration,  and  he  found  the  proof  in  the  following 
ingenious  experiments :  If  an  animal  is  made  practically  fat-free 
by  starvation,  and  then  fed  with  a  foreign,  easily  recognizable 
fat,  as  mutton  fat,  cacao-butter,  line  oil,  this  may  easily  be 
detected  in  the  normal  fat  depots  of  the  body.  Now,  if  such  an 
animal  is  poisoned  with  phosphorus,  or  some  other  substance 
leading  to  marked  fatty  degeneration,  the  fatty  degenerated 
organs  are  found  to  contain  this  foreign  fat.  If,  on  the  other 
hand,  such  animals  were  simply  starved  and  then  poisoned,  fatty 
degeneration  did  not  occur.  Lebedeff^  has  made  similar  obser- 
vations in  starved  human  beings,  with  the  same  result.  The 
previous  investigations  of  Lusk'°  and  his  pupils  on  phosphorus- 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS  117 

poisoning  had  already  denioiistrated  the  infiltrative  character 
of  these  fatty  changes,  and  he  interpreted  them  as  an  attempt  on 
the  part  of  injured  cells  to  keep  themselves  alive.  He  therefore 
speaks  of  sii^ar-hungry  cells. 

An  interestin<i;  observation  was  also  made  by  Fischler,"  who 
carried  soap  solution  through  excised  kidneys,  and  obtained  in 
this  way  the  picture  of  fat  de<ieneration.  He  accomplished  the 
same  by  usinti;  blood,  soap,  and  glycerin.  From  this  it  was  con- 
cluded that  the  fat  is  brought  to  the  parts  in  soluble  form. 

Rosenfeld  found,  further,  that  there  exists  a  distinct  relation 
between  the  glycogen  content  and  fat  degeneration.  The  latter 
does  not  occur  in  the  presence  of  the  former,  and  if  gh^cogen  is 
administered  to  animals  poisoned  with  phloridzin,  the  fat  de- 
generation diminishes.  He  interprets  this  similar  to  Lusk: 
Fat  and  glycogen  furnish  fuel  for  the  purpose  of  defense  against 
toxins,  and  compensate,  therefore,  a  lost  protoplasmic  portion 
of  the  cell.  Rosenfeld,  therefore,  speaks  of  fat  regeneration,  in- 
stead of  fat  degeneration. 

Now,  pathologists  have  always  hesitated  to  accept  the  idea  of 
pure  fat  infiltration  for  all  fatty  changes  in  organs,  and  mainly 
on  morphological  considerations.  You  know  well  that  the  ap- 
pearance of  fat  in  cells  goes  along  in  certain  cases,  just  as  Vir- 
chow  observed  it,  with  protoplasmic  destruction,  and  again  with 
relatively  good  preservation  of  the  cell  constituents.  For  the 
first,  pathological  anatomists  have  retained  the  term  of  fatty 
degeneration,  and  for  the  second,  fatty  infiltration.  ^>ry  soon 
evidence  accumulated  which  again  brought  new  support  to  these 
old  but  perfectly  justifiable  conceptions.  In  the  first  place,  it 
was  found  that  the  apparently  very  clear  conclusive  observations 
of  Rosenfeld  and  others  had  notable  exceptions,  inasmuch  as  in 
some  fatty  degenerated  organs — the  kidneys,  particularly — the 
fat  content  was  not  onlv  not  alwavs  increased,  but  occasionallv 


118  bright's  disease 

actually  diminished!  How  can  this  be  explained?  Explana- 
tion of  this  phenomenon  came  from  another  source. 

If  organs  are  kept  under  entirely  aseptic  conditions,  there 
occurs,  as  you  know,  a  post-mortem  softening.  This  is  especially 
well  illustrated  in  certain  inflamed  organs,  particularly  the  lungs, 
which  are  rich  in  exudate.  This  softening,  or  autolysis,^^  is 
accompanied  by  the  appearance  in  the  cells  and  tissues  of  an 
abundance  of  granules,  somewhat  similar  in  morphological  ap- 
pearance to  the  changes  we  observe  in  the  process  still  called  fat 
degeneration  and  in  late  parenchymatous  degeneration.  These 
small  fat-appearing  droplets  differ,  however,  in  certain  impor- 
tant physical  and  chemical  respects  quite  markedly  from  the 
ordinary  neutral  fat,  i.  e.,  the  combination  of  glycerin  with  a 
fatty  acid  radicle.  Physically,  these  substances  are  charac- 
terized by  double  refraction  of  polarized  light;  chemically,  by 
a  marked  difference  in  constitution  from  ordinary  fat,  and  de- 
composition with  frequent  formation  of  glycerin  phosphoric  acid. 
While  such  bodies  have  been  known  for  a  long  time  and  been 
called  collectively  ^'myelins"  by  Virchow,  they  assumed  now  a 
new  light  and  importance,  and  have  recently  been  the  field  of 
much  active  investigation.^^  They  include  substances,  the  most 
familiar  of  which  are  lecithin,  protagon,  cholesterin.  The}^  have 
also  become  known  under  the  name  of  lipoids,  a  term  introduced 
b}^  Kletzinski  fifty  years  ago,  and  reintroduced  by  Overton. 
Common  to  all  of  them  is  solubility  in  ether,  alcohol,  chloroform, 
benzol.  I  cannot  enter  here,  of  course,  into  a  detailed  discussion 
of  these  Ijodies,  but  I  will  illustrate  their  general  chemical  rela- 
tions. 

Our  knowledge  of  the  chemistry  of  these  substances  is  still 
very  uncertain,  which  is  largety  due  to  the  fact  that  it  has  been 
extremely  difficult  to  isolate  them  in  the  pure  state.  The  entity 
and  constitution  of  some  of  them,  at  least,  are,  therefore,  still 
doubtful  and  uncertain. 


DEGENKHATIVK    AND    EXUDATIVE    NEPHRITIS  119 

Accordin<;-  to  the  iiivesti^-ations  of  lluKlicliuni  and  Jiaii^-,  we 
may  classifv  them  fiisl  :  As  phosphatides,  /.  c,  lipoids  containino- 
nitro^-en  and  phosphorus.  'i\)  Ihis  oroup  helon.i;-  the  lecithins 
;iiid  the  I'elatcd  bodies,  kephahii  in  the  brain,  myehn  and  para- 
myeliii  and  sphyng-omyelin,  occurring;-  also  in  the  brain,  in  e<;o; 
yellow,  in  red  blood-cells,  and  in  the  suprarenals.  These  repre- 
sent mono-amido-mono-phosphatides,  mono-amido-diphospha- 
tides,  di-amido-mono-phosphatides,  and  tri-amido-phosphatide, 
the  latter  a  substance  occurring  in  the  kidney. 

Their  chemical  constitution  is  perhaps  best  illustrated  in  the 
lecithins.  In  order  to  trace  this  structure  we  have  to  synthetize 
the  decomposition  products. 

Commencing-  with  ammonia,  with  which  you  are  all  familiar, 

/H 
N-H  /H 

\H         and  its  hydroxid         N— H 

Ammonium  Ammonium  hydroxid 

we  may  obtain  by  simple  substitution  a  compound  known 
chemically  as  trimethyl-oxy-ethyl  ammonium,  or  more  fre- 
quently as  cholin,  an  ammonium  base,  as  follows : 

/CHo— CHo(OH) 

N-(CH3)3 
\0H 

This  base  may  combine  with  glycerin  phosphoric  acid : 

CHo(OH) 

CHo(OH) 

CHo— 0    \ 

OH-PO, 
OH/ 

in  which  two  of  the  hydrogens  have  been  replaced  by  two  fatty 
acid  radicles,  say  of  the  stearyl  group : 


120  bright's  disease 

CH0-O-C1SH35O 

CH  -0-C,sH350 

CHo— O  \ 
HO-PO 
/CoHH— O    / 

N-(CH3)3 
\0H 

and  we  then  obtain  the  distearyl-lecithin.  It  will  be  plain  from 
this  formula  and  development  that  there  is  more  than  one 
kind  of  lecithin,  depending  upon  the  kind  of  fatty  acid  radicle  in 
the  giycerin-phosphoric-acid  group  of  the  compound.  We, 
therefore,  have  also  palmityl  and  oleyl-lecithins,  and  Thudichum 
regards  it  as  possible  that  two  different  fatty  acid  radicles  may 
enter  into  the  combination,  thereby  increasing  the  number  of 
possible  lecithins. 

All  of  these  substances  occur  in  animal  cells  in  abundance, 
and  their  decomposition  products  are  found  normally  in  traces 
in  the  urine,  ^^  but  under  abnormal  conditions,  particularly  in 
certain  metabolic  and  nervous  disturbances  with  toxic  symptoms, 
cholin  and  glycerin  (organic)  phosphoric  acid  have  been  found 
much  increased  in  the  urine. ^'^ 

The  second  group  is  made  up  of  nitrogenous  but  phosphorus- 
free  lipoids,  the  so-called  cerebrosides,  and  related  to  the  glyco- 
sides, which  form  constituents  of  the  so-called  protagon. 

The  third  and  very  important  group  is  represented  by  the 
non-nitrogenous  and  non-phosphorized  cholesterins,  which  belong 
to  the  terpenes.  These  are  of  very  great  interest,  not  only  on 
account  of  their  wide  occurrence  in  the  animal  and  vegetable 
kingdom,  as  the  so-called  phytosterin,  but  Ijecause  they  par- 
ticularly have  acquired  a  very  great  role  in  the  problems  of  fat 
degeneration  and  fat  infiltration.  The  elder  Beneke  drew  atten- 
tion to  the  abundant  occurrences  of  cholesterin  many  years  ago, 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS  121 

but  not  until  recent  1\'  has  this  importance  })een  properly  valued. 
Chemically,  it  has  the  formula  C2rH4«0,  and  is  a  monovalent, 
simple,  unsaturated,  secondary'  alcohol,  containing  four  saturated 
hydrated  nuclei.  The  chemical  constitution  of  cholesterin 
stamps  it  evidently  as  complicated  terpene,  i.  e.,  isomeric  hy- 
drocarbon of  the  general  formula  C,oHu,.  It  has,  therefore,  no 
chemical  relation  to  the  previously  mentioned  substances  or  the 
fats.  Related  to  the  cholesterins  in  the  animal  body  are  certain 
decomposition  products,  as  kaprosterin,  formed  in  the  gut  from 
the  cholesterin  of  the  bile,  and  further  isocholesterin,  found  in 
lanolin.  Part  of  the  cholesterin  secreted  by  the  bile,  however, 
seems  to  be  reabsorbed  by  the  gut,  similarly  to  the  bile-pigment. 
As  an  example  of  its  wide  distribution  through  the  animal 
body.  I  might  mention  that  it  apparently  forms  an  outer  zone  to 
many  cells,  and  acts  antagonistically  to  cell  solvents.  Thus,  in 
erythrocytes  it  is,  according  to  Ranson,  distinctly  so  to  the  hemo- 
lytic action  of  saponin. ^*^  The  origin  of  cholesterin  in  the  body 
is  so  far  unknown;  it  may  possibly  be  derived  from  the  vegetable 
phytosterin.  Its  natural  history  in  the  body  is  also  unknown; 
but  it  occurs  in  combination  with  fatty  acids,  and  particularly  as 
esters.  Protagon,  which  I  mentioned  before,  has  had  a  ver\' 
disturbed  history.  First  discovered  by  Liebreich  in  1865,  and 
pronounced  an  entity,  it  appears  now  to  be  mostly  a  mixture  of 
phosphorized  and  phosphorus-free  lipoids,  particularly  sphyn- 
gomyelin  and  phrenosin.  A  protagon-like  substance  occurs  in 
nephritis,  according  to  Lohlein^"  and  others,  in  crv'staUine  form 
in  the  intertubular  tissue  and  the  lymphatics.  It  is  there 
probably  derived  from  an  abundant  disintegration  of  cell  proto- 
plasm. It  is  doubly  refractive,  and  gives  the  sudan  III  fat  stain, 
soluble  in  alcohol  and  insoluble  in  acids  and  alkalis.  Panzer,^^ 
however,  has  shown  that  this  is  probably  also  an  ester  of  choles- 
terin with  fattv  acids. 


122  bright's  disease 

It  has  developed,  therefore,  that  fat-related  substances  may 
appear  during  the  disintegration  of  the  protoplasm  of  all  cells, 
and  that  some  of  these,  on  further  decomposition,  may  yield 
neutral  fat.  This,  under  such  conditions,  is  therefore  not  neces- 
sarily brought  to  the  parts  from  distant  depots. 

Now,  what  does  all  this  represent,  and  what  is  its  relation  to 
fat  degeneration  and  fat  infiltration? 

In  the  course  of  investigation  into  this  problem  some  very 
interesting  points  developed.  Rosenfeld  as  the  first  drew  at- 
tention to  the  fact  that  the  microscopic  appearances  and  valua- 
tion of  fat  contents  of  an  organ  are  unreliable,  and  that,  there- 
fore, chemical  and  morphological  results  do  not  cover  each  other 
in  fat  determination.  Healthy  and  fatty  kidneys  may  not  show 
their  fat  contents  at  all,  even  if  this  amounts  to  23  per  cent. 
More  curious,  however,  is  the  fact  that  kidneys  of  the  same  fat 
contents  (17.9  to  18.2  per  cent.)  may  appear  at  one  time  healthy, 
at  another  extremely  fatty.  Kidneys  with  even  a  diminished 
amount  of  fat,  say,  16  per  cent.,  may  seem  to  us  at  times  extremely 
fatty.  That  this  is  not  peculiar  to  the  kidney  was  shown 
by  Bossard  and  Schmoll  and  Rosenthal. ^^  The  latter  could  not 
demonstrate  morphologically  with  osmic  acid  and  sudan  any 
fat  in  cheesy  tuberculous  masses,  while  ether  extracted  con- 
siderable amounts  of  soap  and  cholesterin.  Klotz,^°  from  Adami's 
laboratory,  has  only  recently  pointed  out  that  at  least  part  of  the 
myelins  in  the  kidney  exist  as  soaps  of  oleic  acid,  and  that  such 
fatty  compounds  are  not  readily  demonstrated  by  the  ordinary 
staining  with  sudan  III,  but  can  be  obtained  by  extraction 
with  alcohol.  It  is,  therefore,  evident  that  the  presence  of  fat 
and  fat-like  substances  may  not  always  be  visible ;  on  the  other 
hand,  may  become  visible,  with  relatively  small  quantities,  not 
exceeding  the  normal.  From  the  foregoing  it  follows  that  the 
morphological  appearance  of  fat  in  the  organs  means  not  neces- 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS  123 

sarily  inc-rease  in  fat,  hut  a  molecular  ph\'sical  decoii.stitutioii  of 
the  cell,  wherel)v  fat  originally  contained  and  concealed  in  the 
structure  of  the  protophism  appears  free  to  us.  Kraus,"^  and 
particularly  Alhreclit.-"  whose  ideas  I  have  already  presented  in 
connection  with  i^arenchymatous  degeneration,  assume  for  its 
explanation  that  protoplasm  exists  normally  as  a  fluid  pulp,  an 
emulsion,  which  contains  fatty  substances  so  finely  divided  that 
they  are  invisible.  Kraus  draws  attention  to  the  fact  that  neutral 
fluid  fat  does  not  readily  emulsify,  but  does  so  as  soon  as 
some  fatty  acid  is  added.  This  is  explainable  by  the  supposition 
that  fluid  fat  is  a  solution  of  fatty  acid,  whose  molecules  are 
equally  distributed,  as  in  all  solutions,  between  those  of  the 
neutral  fat.  If  this  mixture  is  brought  into  contact  with  an 
alkali,  these  molecules  diffuse  into  it  and  form  soaps,  which  unite 
as  a  honeycomb  (Biitschli),  inclosing  within  it  the  fluid  fat  in  the 
form  of  drops.  Albrecht's  "  tropfige  Entmischung,"  or  myel- 
inic deconstitution,  w^hich  we  have  reviewed,  would  l^e  of  a 
similar  nature,  although  it  also  includes  important  changes  in 
the  protein  constituents  of  the  protoplasm. 

The  old  conception  of  Virchow,  who  spoke  of  a  direct  trans- 
formation of  protein  into  fat,  has  been  discarded,  therefore,  and 
Kraus  has  reintroduced  the  term  fatty  metamorphosis,  by  which 
is  understood  a  physical  deconstitution  of  the  cell  protoplasm, 
with  the  liberation  of  fat-similar  substances. 

A  different  view,  however,  is  entertained  by  Aschoff,^'^  who 
still  regards  the  vital  fat  processes  as  infiltrative  in  character. 
In  favor  of  this,  he  puts  forw^ard  the  coexistence  of  isotropous 
and  anisotropous  drops  in  the  same  cells,  the  occurrence  of 
anisotropous  substances  in  cells  which  show  no  evidence  of 
degeneration,  and  particularly  the  resorption  of  anisotropous 
drops  by  the  endothelial  lymph-cells  of  the  gall-bladder  in  long- 
continued  bile  stasis;  he  holds,  further,  that  in  abscess  formation 


124  bright's  disease 


and  durino;  degenerative  inflammatory  lesions,  as  in  long-con- 
tinued nephritis,  cholesterin  is  set  free,  and  either  replaces  the 
glycerin  with  the  formation  of  lipoids,  or  is  taken  up  by  cells  as 
completed  cholesterin  ester  with  other  neutral  fat.  He  therefore 
speaks  of  two  groups  of  fat  infiltrations:  one,  the  glycerin-ester- 
fat  infiltration,  and  the  other  the  cholesterin-ester-fat  infiltration. 
Aschofi"  differentiates  these  changes  definitely  from  the  so-called 
postmortem  or  autolytically  originating  myelins.  The  latter, 
he  states,  almost  always  lack  anisotropism  in  contradistinction  to 
the  intravital  forms.  The}'  are  not  fatty  in  reaction,  and  there- 
fore lack  the  characteristic  stains  of  these  substances  with  sudan 
III,  Scharlach,  Xileblue,  and  osmic  acid.  But  he  admits  that 
during  autotysis  fatty  substances  of  the  glycerin  and  cholesterin 
type,  which  were  stored  in  the  cells  during  vital  processes,  may 
appear. 

There  are  one  or  two  other  points  which  deserve  considera- 
tion. 

Rubow-'^  showed  that  the  percentage  increase  of  fat  in  the 
fattily  degenerated  heart  was  relatively  very  low — 1.6  per  cent, 
of  the  moist,  8  per  cent,  of  the  dr\;,  muscle  substance,  amounting 
to  only  about  3  per  cent,  of  the  fresh  muscle,  not  more  than  5  to 
9  gm.  for  the  whole  heart.  ]\Iany  times  it  is  less.  These 
figures,  Rubow  holds,  can  be  explained  perfectly  on  the  strength 
of  the  normal  fat  contents  of  the  blood  (0.1  to  1.4  per  cent.), 
which  have  not  been  normally  taken  up  b}'  the  injured  protoplasm 
of  the  cells.  As  reason  for  this  inability  of  fat  reabsorption  by 
the  cells  he  regards  diminution  of  alkalinity  of  the  plasma. 
Contributors'  evidence  to  this  view  may  be  gained  from  the  fact 
that  an  increase  of  acid  production  has  been  actually  noted  in 
conditions  that  are  very  apt  to  be  associated  with  fatty  changes, 
and  that  fatty  acids  are  formed  during  autolysis.  Rubow  also 
regards  the  fatty  cell  as  an  injured  cell,   which,  under  toxic 


DEGENERATIVE    AND    EXUDATIVH    NEPHRITIS  12") 

iiiflucuc'os  and  a  perverted  nietal)olisin,  ])r()du('es  inoj-e  acid  and 
probably  disehar<2;es  less.  As  a  result,  ciiminished  alkalinity 
of  the  ('(^11  plasma  follows,  with  inabilil\'  of  fat  absorption, 
Oswald^''  has  pointcvl  out  that  the  ideas  of  liuhow  are  really  not 
opposed  to  those  of  Rosenfeld,  inasmuch  as  it  may  be  supposed 
that  the  blood  leaves  its  fat  in  the  degenerating-  orj;ans  to  later 
carry  more  fat  to  it  from  the  distant  fat  depots  of  the  body. 

Now,  to  sum  up:  From  the  foregoing-  it  appears  that  the 
occurrence  of  fat  in  the  or«»;ans  is  not  of  uniform  character,  and 
also  not  of  uniform  derivation.  It  may  occur  first  as  a  transpor- 
tation of  material  to  cells  for  the  purpose  of  supplying  an  easily 
combustible  substance,  or,  I  take  it,  as  a  compensatory  process 
to  relieve  a  loss  of  protoplasmic  parts  of  the  cells,  which  takes 
place  either  as  a  direct  destruction,  or  by  quantitative  inter- 
ferences with  the  cell  nutrition,  as  durin<>;  inactivity  and  simple 
atroph}'-  of  organs.  Whenever,  in  such  cases,  restitution  of 
protoplasmic  material  becomes  impossible,  fat  is  substituted. 
This  accumulation  is  aided,  undoubtedly,  in  many  cases,  by  in- 
ability to  burn  fat  properly.  The  nature  of  this  fat  is  largely 
neutral,  isotropous  fat  glycerin  esters.  But  when  this  process 
becomes  associated  with,  and  takes  place  under,  conditions 
leading  to  rapid  cell  destruction,  it  has  added  to  it  anisotropous 
cholesterin  esters  and  other  lipoids  which  either  originate  in  the 
cell  itself  or  are  brought  to  it  from  other  cellular  sources. 

On  the  other  hand,  in  severe  degenerations,  necrosis,  and 
autolysis  of  cells,  there  occurs  from  the  start  a  severe  internal 
revolution  within  the  protoplasm  of  the  cell,  leading  to  general 
disorganization  of  the  latter,  with  the  setting  free  of  fat-related 
substances;  these,  on  further  decomposition  and  re-synthesis, 
may  later  give  rise  to  neutral  fats,  and  lead  to  fat  infiltration  of 
other  cells. 

Fat  infiltration  and  fat  metamorphosis  are  then  two  inti- 


126  bright's  disease 

mately  connected  and  related  conditions,  which  depend  either 
on  the  existence  of  hving;  cells  or  on  dead  or  dying  and  dis- 
organizing cells.  The  complicated  nature  of  nutritive  disturb- 
ances in  organs  makes  a  combination  of  both  of  these  at  times 
probable,  and  the  diminished  alkalinity  of  the  blood  may  well 
be  an  influencing  factor. 

Under  normal  conditions  a  moderate  degree  of  fat  infiltration 
in  the  kidney  has  been  noted  by  von  Hansemann,  and  we  can 
easily  conceive  of  this.  But,  on  the  other  hand,  the  myelinic 
disintegration  of  cells,  and  the  occurrence  of  protagon,  choles- 
terin,  and  related  bodies  in  considerable  amount,  must  always  be 
of  pathological  origin. 

Bearing  in  mind  the  experiences  of  this  excursion,  and  to 
return  to  our  morphological  considerations,  you  will  be  in  a 
position  to  appreciate  the  great  individual  variations  which  the 
kidney  under  consideration  may  present.  The  fat  may  either  be 
recognizable  in  patches,  streaks,  or  cover  larger  areas;  it  may  be 
confined  to  certain  parts  of  the  tubules,  particularly  the  loops 
and  proximal  end,  or  it  ma}^  be  diffuse,  involving  the  whole 
tul^ule,  although  in  varjdng  degree.  In  the  beginning  of  the 
process,  fat  appears  in  the  peripheral  portion  of  the  cell  near  the 
tunica  propria.  A'VTiile  these  changes  are  more  prominent  in 
the  epithelium  of  the  tubules,  they  may  sometimes  reach  a  high 
degree  in  the  glomerulus. 

I  turn  now,  secondty,  to  the  further  events  which  take  place 
in  the  glomeruli  and  tubules  subsequent  to  the  inflammatory 
changes  with  which  we  have  already  become  acquainted. 

In  the  glomerulus  we  had,  you  remember,  degeneration  of  the 
lining  epithelium  and  endothelium  of  the  tuft,  with  proliferation 
of  the  latter,  exudation  within  it  and  into  the  capsule,  and  at 
times  proliferation  of  the  epithelial  cells  advancing  from  the 
periphen^^  toward  the   center.     The  whole  tuft  becomes  thus 


DEGENERATIVE    AND   EXUDATIVP:    NEPHRITIS 


127 


Ml 


9( 


Fig.  30. — Higli  magnification  of  glomerulus,  showing  lesion  advanced  to  that  of  Fig. 
14.  The  flattened,  fibrillar,  cap.sular  cells  are  seen  to  fuse  with  the  cells  of  the  atropine 
tuft.     Few  unusually  large  capillary  loops  show  in  cross-section. 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS  129 


Fig.  31. — The  whole  globule  has  become  involved  in  a  hyaline  transformation. 


10 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS 


131 


V^-^ 


%^v 


^^^^2^^%^ 


Fig.  32. — Completed  hj'aline  transformation  of  a  glomerulus  with  few  nuclear  remnants. 
Surrounded  bv  very  cellular  fibrous  tissue. 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS  133 

iiiipcniicahk'.  luilaininatorv  lliroinhi  funu  witliiii  the  capillaries, 
while  the  cellular  exudate  fuses  with  necrotic  cellular  material 
and  unites  the  capillar}'  lobules  of  the  tuft  and  the  capsule  to  a 
mass.  This  leads  to  several  results.  If  the  tuft  has  been  shut 
off  from  all  communication  with  afferent  and  efferent  vessels, 
it  necessarily  disintegrates  rapidly,  so  that  its  parts  break  off 
into  fragments  and  are  washed  away.  If,  however,  some  com- 
munication with  the  outside  vessels  has  l)een  retained,  a  rather 
irregular  destruction  of  the  glomerulus  follows:  and  some  of  the 
still  permeable  capillaries,  particularly  near  the  hilus  of  the  glom- 
erulus, imdergo  compensatory  dilatation.  The  endothelial  cells 
of  these  capillary  walls  sw^ell,  w^hile  those  of  the  collapsed  areas 
undergo  fusion.  C  apillary  lobules  are  thus  o]:)literated  and  dis- 
connected from  the  still  permeable  portions  of  the  tuft,  and  fall 
to  one  side,  to  undergo  rapid  disintegration.  Finally,  the  whole 
of  the  tuft  filled  with  endothelial  nuclei  and  hyaline  masses  and 
some  leukocytes,  breaks  up  into  disintegrating  lol^ular  remnants, 
and  the  capsule  collapses. 

Where  the  capsular  epithelium  has  undergone  marked  pro- 
liferation, these  cells  become  flattened,  stringy,  fibrillar  in  ap- 
pearance, fuse  wdth  the  other  cells  of  the  tuft,  or.  stagnant, 
retained  albuminous  exudate  to  hyaline  material.  It  is  pos- 
sible that  endothelial  cells  of  the  obliterated  tuft  may  take 
part  in  a  similar  fibrillar  and  subsequent  hyaline  transformation 
(Figs.  30,  31,  32).  The  destruction  of  the  glomerulus  and  the 
Malpighian  body  is  usually  not  so  violent.  It  may  result  from 
fil)rinous  adhesion  of  the  capillar}'  loops  to  each  other  and  to  the 
epithelium  of  the  capsule.  Lohlein  considers  adhesion  by  des- 
quamated capsular  cell  detritus  sufficient.  Thus  immobilized, 
a  gradual  connective-tissue  synechia  of  capsular  connective 
tissue  and  glomerulus  occurs.  The  connective  tissue  grows  into 
and  separates  the  fused  glomerular  lobules.      Ziegler.   Engel, 


134  eright's  disease 

and  Herxheimer  have  drawn  attention  to  similarity  of  these 
changes  with  those  observed  in  serous  membranes. 

Again  in  protracted,  less  brusque  cases,  the  glomerular  lobes 
are  transfornied  b}^  hyaline  swelling  of  the  loops  and  endothelial 
and  possibly  epithelial  proliferation  into  a  compact,  plump, 
first  cellular,  then  hyaline,  body.  Amyloid  material  is  deposited 
in  the  capillary  loops,  particularly  in  constitutional  diseases, 
associated  with  hyaline  infiltration  of  other  organs  and  vessels. 
According  to  Wichman  and  Martland,  amyloid  material  infil- 
trates the  parts,  while  the  cells  are  not  transformed  into  amy- 
loid, and  Hueter  finds  the  amyloid  deposited  within  the  lumen 
of  the  capillar}^  vessels.^' 

Other  processes  may  also  lead  to  hyaline  transformation  of 
the  Malpighian  body,  as  the  result  either  of  lack  of  proper  blood- 
supply  of  the  glomerular  tuft  or,  as  Ponfick  believes,  as  the  result 
of  stagnation  within  and  obliteration  of  the.  convoluted  tubules. 
In  such  events  the  epithelium  and  endothelium  of  the  tuft 
become  pale,  turbid,  swell,  and  fuse  to  a  structureless,  hyaline 
body.  This  is  occasionally  initiated  by  oedematous  imbibition 
of  the  parts,  so  that  the  glomerulus  fills  the  distended  cap- 
sule. A  common  event  is  connective-tissue  invasion  from  the 
capsular  tunic,  which  pushes  before  it  a  gradually  atrophying 
capsular  epithelium  (Fig.  38).  According  to  some  of  Dr.  Milne's 
observations,  this  seems  to  be  the  case  in  glomeruli  where 
originally  the  exudate  lifts  the  epithelial  cells  off  the  basement 
membrane  and  pushes  them  before  it  toward  the  tuft.  Later, 
this  exudate  is  replaced  by  gradually  thickening  capsular  con- 
nective tissue,  which  occasionall}"  still  shows  toward  the  tuft  a 
ver}'-  thin,  almost  endothelial-like,  cellular  lining  (Fig.  8  and 
Figs.  39  and  40). 

Similar  is  the  fate  of  the  glomerulus  in  cases  when,  as  we  saw 
before,  only  a  portion  of  the  tuft  has  been  firmly  attached  by 


DEGENEHAin  K    AM)    EXUDATIM:    NEPHRITIS 


135 


Fig.  33.— In  one  glomerulus,  inflammatoiy  attachment  to  cap.sule,  with  localized  peri- 
glomerular  thickening;  increase  of  endothelial  nuclei  in  Ijoth  glomeruh.  Dilatation  of 
cap.sule.      X  185. 


DEGENERATIVE    AND    EXUDATIVE    NEPHIUTIS 


137 


t4  V  *  ^^^i^l:'^^$^^ 


^i'^r 


^ 


Fig.  34. — Various  stages  of  hyaline  glomerular  replacement.     Hj'aline  casts  in  tul)ule? 

X  200. 


Fig.  35. — One  glomerulus  with  complete  hyahne  atrophy.     Hyaline  change  in  a  glomerulus 
commencing  in  the  part  attached  to  capsule.      X  220. 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS 


139 


k.?  1 


Fig.  36. — Complete  hyaline  atrophy  of  a  glomerulus.     In  the  neighborhood  a  very  much 
thickened  and  almost  obliterated  vessel.      X  400. 


Fig.  37. — Advance  1  fibrous  invasion  and  replacement  of  a  glomerulus.     An  adjoining  rela- 
tively healthy  glomerulus  in  compensatory  functional  hypertrophy.      X  200. 


DEGENEUATIVE    AND   EXUDATIVE   NEPHKITIS 


141 


/'■ 


^ 


Fig.  38. — Gradual  peiiplicral  libnilar  invasion  of  a  hyaline  glomerulus. 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS 


143 


Fig.  39. — Capsular  thickening  with  extension  of  Uning  cells  before  it  and  fibrous 
replacement  from  an  attached  point  of  the  base  of  the  tuft.  Complete  hyaline  tran.sforma- 
tion  of  a  glomerulus.     Some  of  the  tubules  filled  with  newly  formed  cells.      X  220. 


Fig.  40. — Advanced  and  invading  fibrous  capsular  thickening  of  a  glomerulus.      X  220. 


DEGENKRATIXK    AND    EXUDATIVE    XEIMIKITIS 


145 


^^M^> 


Fie.  41. — New  cylindrical  epitholium  in  tnlniles  in  productive  nephritis. 


11 


DE(iKNKl{A'riVI<:    AND    KX  UDA'I'I  VK    NKIMIIUTIS  147 

exudate  to  a  j);irt  of  the  (*n})sule,  which  is  usually  close  to  the 
entrance  and  exit  of  the  vessels,  although  it  may  occur  in  other 
parts  of  the  capsule  as  well.  Then  it  ^ives  rise  very  soon  to  a 
fibroblastic  proliferation  of  the  connective  tissue  at  the  periphery 
of  \\\v  capsule,  l^ut  this  is  not  only  confined  to  the  periji;lomeru- 
lar  tissue,  which  i^radually  thickens  by  the  concentric  deposit  of 
fibrous  tissue  layers,  but  it  invades  the  adherent  tuft,  and,  grad- 
ually growing  into  it,  replaces  this  by  slowly  maturing  fibrous 
connective  tissue.  As  an  end-result  the  glomerulus  has  again 
been  obliterated.  It  is  interesting  to  note  that  this  fibrous  in- 
vasion and  replacement  of  the  glomerulus  take  place  from  the 
spot  of  adhesion  to  the  capsule  (Fig.  33).  The  connective  tissue 
in  the  glomerulus,  however,  very  soon  suffers  from  the  same  nu- 
tritive disturbances  that  the  obliterated  tuft  experienced,  and, 
therefore,  becomes  gradually  transformed  into  homogeneous 
material  which,  by  fusion  with  the  remaining  tuft  structures, 
gives  to  the  whole  glomerulus  a  characteristic  hyaline  appear- 
ance. Early  in  the  process  bands  of  connective  tissue  can  be 
seen  to  grow  into  and  separate  hyaline  or  amyloid  masses  in 
glomeruli.  This  hyaline  material  still  encloses  cellular  and 
particularly  nuclear  remnants.  Later  even  these  disappear,  and 
there  remains  a  dead-looking,  non-functionating  globule,  sur- 
rounded l^y  somewhat  better  preserved,  usually  loose  and 
stretched,  connective  tissue.  This  capsular  connective-tissue 
type  of  glomerular  replacement  has  lately  been  particularly 
emphasized  by  Herxheimer-^  (Figs.  33,  34,  35,  36,  37).  All 
types  of  fibrous  glomerular  replacements  are  associated  with 
concentric  periglomerular  connective-tissue  thickening.  This  is 
rich  in  elastic  fibers. 

We  see  that  in  the  hyaline  transformation  of  glomeruli  all 
the  component  structures  are  involved,  capsular  epithelial,  capil- 
lary endothelial,  capsular  fibrous  connective  tissue,  assisted  by 


14S  bright's  disease 

any  exudate  which  may  be  present.  The  resulting;  hyaline 
bodies  are  of  different  composition.  This  is  well  illustrated  by 
van  Gieson's  stain,  which  gives  to  the  connective-tissue  hyaline 
a  distinct  red,  to  the  others  a  yellow  color.  According  to 
Herxheimer,  the  yellow  glomerular  hyaline  undergoes  gradual 
resorption,  while  the  red  connective-tissue  h3^aline  is  more  resis- 
tant. A  late  result  is  calcareous  infiltration  of  the  glomeruli — in 
my  experience  not  a  very  frequent  process.  Baum  has  drawn 
attention  to  the  fact  that  many  of  these  calcareous  small  nodules 
are  really  calcified  cj^'sts,  of  which  I  shall  speak  later. 

Coincident  with  all  these  changes,  which,  as  you  appreciate, 
are  diffusely  and  very  unevenly  distributed  throughout  the 
kidne}',  go  necessarily  marked  alterations  in  the  size  of  the  glom- 
eruli. The  best  preserved  glomeruli  very  soon  undergo  func- 
tional compensator}^  hypertrophy,  the  tuft  enlarges  to  not  only 
fill  the  capsular  space,  but  to  actually  stretch  it,  and,  therefore, 
enlarges  the  whole  secreting  apparatus.  Unfortunately  for  the 
individual,  such  glomeruli  are  later  apt  to  be  overtaken  by  the 
same  fate  as  the  others.  The  atrophying  and  degenerating 
glomeruli,  on  the  other  hand,  show  much  diminution  in  size,  and 
the  final  h3"aline  remnants  are  usually  smaller  than  the  healthy 
glomerulus. 

Xow,  the  tubules  also  present  gradually  a  very  varied  picture. 
As  their  epithelium  undergoes  different  states  of  degeneration 
and  desquamation,  they  enlarge,  and  become  filled  with  cells 
and  cellular  debris,  leukocytes,  red  blood-cells,  and  blood-pig- 
ment. All  these  may  fuse,  as  we  saw,  into  cellular,  hyaline,  or 
waxy  casts.  Fatty  casts,  of  course,  become  frequent.  Grad- 
ually these  masses  are  pushed  along,  stagnating  permanently 
or  for  a  time  on  their  downward  way.  This  stagnation  is  aided 
})y  inflammatory  obliteration  of  lymphatics.  Proliferation  of 
the  epithelium  is  here  also  a  prominent  feature,  and  of  the  same 


DKCiENEHATIVE    AND    EXUDATIVE    NEl'ilKllIS  149 

ty[)os  which  we  met  lu^foro,  /.  r.,  iiifijiiiiinatory  aiifl  ro<2;onorativr'. 
IiiflatiiiiiMtory  hy|)('i'|)la.sia  of  cpithcliuin  occairs  most  ahuiKhmth' 
ill  the  loops,  uiKloubiedl}'  because  the  .sta<;iiation  of  necrotic 
masses  irritates  and  demands  pha<;ocytic  activity.  In  the  con- 
N'ohiled  liihiilcs  il  usuMhy  remains  confined  to  the  t  uhulnr  \\;ili, 
and  leads  to  many  mult  iimclejir,  hiri^c,  itrcuulnr  cells,  with,  not 
infr(M|U(Mit  ly,  fusion  and  o\'er^TOwtli  to  mult  i nuclear  ,iiiant-cells 
{V'\i^.  ()).  'Hiis  proliferation  may  occur  by  mitosis,  but  accordin*;- 
to  my  observations  by  far  most  frequently  by  amitotic  division, 
and  I  would  put  this  latter  down  as  the  rule  for  the  multiplica- 
tion of  renal  epithelium.  In  clear,  or  at  least  relatively  clear, 
tubules  the  epithelium  regenerates,  but  in  an  unusual  manner. 
This  newly  formed  epithelium,  particularly  well  observed  in  the 
convoluted  tubules,  is  frequently  not  of  the  normal,  lii.iA'h,  dis- 
tinctly striated,  granular,  and  protruding  type,  but  of  a  low, 
smooth  protoplasmic,  in  places  syncytial,  in  others  endothelial- 
like  formation.  The  lumen  of  such  tubules  appears,  therefore, 
much  larger  than  in  the  normal  kidney.  Again,  in  some  tubules 
the  epithelium  becomes  high,  narrow,  and  distinctly  cylindrical 
(Figs.  28  and  41). 

This  newly  formed  epithelium  is  of  great  interest  and  im- 
portance, for  the  questions  of  the  cause  of  this  atypical  formation 
and  its  function  immediately  present  themselves.  That  glandu- 
lar cells,  when  their  environment  changes,  also  change  their  t^^pe, 
is  not  a  \w\v  or  isolated  occurrence  here,  l)ut  it  is  well  known  that 
in  the  sclerotic  lungs,  for  instance,  the  alveoli  become  tubular, 
and  their  lining  epithelium  cuboidal;  the  same  conditions  prevail 
in  the  sclerotic,  productive  inflammations  of  the  liver,  and 
Milne"-'  has  shown  that  the  so-called  newly  formed  bile-ducts  in 
the  cirrhosis  of  the  liver  represent  in  reality  old  bile-capillaries, 
which,  under  the  influence  of  the  new  environment,  have  changed 
their  cell  type.     The  same  conditions  prevail  in  the  kidney,  and 


150  bright's  disease 

the  influence  of  so  many  and  variable  conditions  which,  you 
appreciate,  enter  into  this  new  environment,  accounts  in  no  small 
degree  for  the  many  atypical  cell  forms  which  we  observe  during 
the  inflammatory  hyperplasia.  Ultimately,  when  conditions 
become  more  settled,  a  generally  uniform,  although  morpholog- 
ically different,  regenerated  epithelium  forms  as  the  result  of 
more  permanent,  but  changed,  environment. 

Of  great  practical  interest  is,  of  course,  the  associated  func- 
tional change  that  must  go  hand  in  hand  with  such  a  morpholog- 
ical transformation.  About  this  we  know  very  little,  but  it 
seems  as  if  certain  complicated  and  obscure  functional  changes, 
which  are  always  observed  late  in  these  nephrites,  might  possibly 
be  traced,  not  only  to  the  inflammatory  involvement  and  ana- 
tomical rearrangement  of  the  parts,  but  also  to  the  loss  of  nor- 
mal and  the  production  of  entirely  new,  secreting  cell  types.* 

I  shall  refer  to  these  matters  again  in  the  discussion  of  the 
so-called  contracted,  or  interstitial,  better  termed,  productive, 
nephritis,  where  these  morphological  and  functional  changes  are 
most  prominent  and  characteristic.  Considerable  variations  in 
size  of  the  tubules  occur.  Some  are  very  much  larger  and  di- 
lated, either  as  the  result  of  functional  hypertrophy,  or  as  the  re- 
sult of  stoppage  of  cellular  masses  with  stagnation  of  fluid  above. 
Others  again  appear  collapsed,  and  atrophy  for  reasons  which 
we  will  presently  discuss.  This  leads  directly  to  the  question  of 
the  result  of  such  changes  in  glomeruli  and  tubules  upon  the 
kidney  substance.  Glomerulus  and  tubule  are,  as  you  appre- 
ciated, a  unit  from  the  anatomical  and  physiological  standpoints. 
A  permanent  injury  to  one  will  necessarily  involve  the  other. 
So  it  happens  that  the  tubule  whose  glomerulus  has  been  lost  in 
either  of  the  ways  just  described  will  collapse,  atrophy,  and  ulti- 

*Thi.s  has  Vjeen  demonstrated  in  this  institute  for  some  time,  and  recently  F.  Miiller 
(I.  c.)  has  drawn  attention  to  a  similar  observation.  But  it  is  really  not  at  all  infrequent, 
more  so  the  rule. 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS  1")1 

nuitely  he  lost.  On  the  other  hand,  a  lon<;-('ontinued  blocking 
of  the  tubule  in  any  portion  of  it,  and  particularly  frequent  in  the 
region  of  the  loops,  either  ])y  cellular  masses,  detritus,  and  es- 
pecially by  lirnily  attached  casts,  will  soon  lead  all  the  structure 
above  the  point  of  occlusion  to  the  same  fate.  While  this  has 
long  been  recognized  as  a  factor  in  the  loss  of  kidney  structure 
in  these  lesions,  it  has  recently  been  particularh'  emphasized  by 
Ponfick-'^  as  an  important  cause  for  the  waste  of  parenchyma. 
Indeed,  Ponfick  goes  so  far  as  to  hold  that  much  of  the  glomeru- 
lar atrophy  and  loss  must  be  attributed  to  a  blocking  of  the  tu- 
bules at  a  considerable  distance  below  then-  origin.  There  can 
be  no  question  that  both  of  these  mechanical  factors  are  largely 
responsible  for  the  gradual  l)ut  progressive  loss  of  substance, 
but  they  are  much  aided  in  it  by  the  results  of  the  infiammator}^ 
condition  in  the  intertubular  substance,  which,  by  obliteration  of 
lymphatics  and  capillaries,  seriously  interferes  with  the  nutrition 
of  the  parts.  These  I  will  consider  in  a  moment.  But  before 
doing  so,  it  must  be  appreciated  that,  as  a  result  of  this 
irregular  loss  of  substance,  the  kidney  now  begins  to  show 
areas  of  collapsed  parenchyma,  between  better  preserved  and 
even  swollen  parts.  The  surface  becomes,  therefore,  progres- 
sively slightly  irregular,  puckered,  and  this  appears  primarily 
and  more  prominently  in  the  cortex.  At  this  point  the  capsule 
still  peels  rather  easily.  However,  this  loss  leads  now  to 
certain  other  changes,  which  alter  still  more  the  appearance 
and  anatomy  of  the  organ.  They  take  their  origin  and  pur- 
sue their  development  particularly  in  the  intertu])ular  tissue, 
and  spread  in  a  streaky  and  later  diffuse  fashion  throughout 
the  whole  organ.  We  must,  therefore,  proceed  now  to  consider 
the  fate  of  this  intertubular  tissue  from  the  time  we  left  it  in  the 
process  of  degeneration  and  exudation.  The  fact  that  lym- 
phatics and  tissue  spaces  are  here  not  cleared,  but  continue  to  be 


152  bright's  disease 

blocked  with  fatty  and  cellular  masses,  while  the  inflammatory 
oedema  continues,  leads  very  soon  to  loss  of  these  cellular  ele- 
ments, followed  by  a  proliferation  of  endothelial  cells  within 
these  channels  and  the  appearance  of  lymphocytic  (polyblastic, 
leukocytoid)  and  fibroblastic  cells  without.  The  cells  thus  pro- 
duced are  partly  phagocytic  and  partly  reconstructive ;  that  is,  a 
certain  number  aid  in  clearing  the  path  for  the  development  of 
fibroblastic  cells.  While  this  is  primarily  confined  to  the  inter- 
tubular  substance,  and  local,  it  soon  assumes  greater  dimensions 
in  all  areas  where  adjoining  tubules  and  glomeruli  are  wasting 
and  atrophied.  It  stands  to  reason  that  this  thickening  and 
obliteration  of  the  channels  of  nutrition  and  reabsorption  must 
also  interfere  with  the  tubules  and  glomeruli,  so  that,  in  my 
opinion,  these  two  changes  interact  and  go  hand  in  hand. 

Now,  as  the  fibroblastic  cells  mature,  the  intertubular  con- 
nective tissue  becomes  less  cellular,  but  thicker,  and,  by  replace- 
ment of  atrophied  parenchyma,  bands  of  connective  tissue 
develop  leading  to  more  or  less  firmly  contracting  scars.  By 
growth  on  the  surface,  the  capsule  becomes  now  irregularly  ad- 
herent, so  that  it  can  be  removed  only  with  great  difficulty,  and 
usually  takes  some  of  the  parenchyma  with  it.  As  these  changes 
are  most  pronounced  in  the  cortex,  this  suffers  the  most.  It 
becomes  very  irregular,  granular,  cicatrices  divide  better  pre- 
served areas,  and  the  normal  markings  have  almost  entirely 
disappeared,  giving  way  to  a  bizarre  arrangement  and  mottled 
appearance  which  varies  much,  and  depends  largely  upon  the 
condition  of  the  vascular  apparatus  (Fig.  42). 

Occasionally,  but  not  frequently,  the  connective-tissue  for- 
mation is  very  diffuse,  without  formation  of  thick,  contracting 
scars;  the  surface  therefore  remains  smooth,  although  the  kidney 
shrinks.  Both  types  are  now  recognized  under  the  name  of 
secondary  contracted  kidne^^ 


CM 


-1 


Fig.  42. — Nephritis  degenerativa  productiva,  with  an  old  healed  infarct  scar.  A 
small  fibroma  in  one  of  the  medullar^'  pyramids,  weight  200 gms.  (From  a  woman,  fifty- 
three  years  old.)  Generally  swollen,  but  mieven  and  scarred  surface,  vrith  collapse  of 
renal  substance  and  irregular  fibrous  tissue  growth  affecting  the  cortex  very  generally.  On 
section,  the  parenchyma  grayish,  in  places  yellowish  (fattj^),  glomerular  rows  obhterated 
or  distorted,  with  formation  of  prominent  compensatory'  vascular  chaimels.  A  large  piece 
of  cortex  lost  as  the  result  of  a  healed  infarct,  at  its  base  a  cyst.  This  kidney  also  showed 
evidences  of  a  superadded  venous  congestion.  Patient  had  a  terminal  fibrinous  pericar- 
ditis. 


DEGENERATIVE    AND    EXl'DATIVE    NEPHRITIS  153 

As  tiie  condition  of  the  vascular  apparatus  is  of  much  conse- 
quence in  the  fate  and  appearance  of  such  a  kidne\',  we  must 
now  pay  some  attention  to  it .  The  vascuhirity  of  the  kidney 
durin<;-  the  process  of  such  a  nephritis  may  be  influenced  in  two 
ways:  first  and  directly,  hv  inflammatory  changes;  second  and 
indirectly,  by  chan<!;es  in  the  tj;eneral  circulation,  which  result 
from  the  effects  of  the  nephritic  lesions  on  the  individual.  We 
have  seen  before  how  in  certain  inflammatory  lesions  the  affinity 
of  the  toxic  excitant  is  particularly  found  and  accentuated  in 
the  blood-vessels :  abundant  diapedesis  of  red  blood-cells  occur, 
hemorrhages  and  even  extensive  hemorrhaoic  extravasations. 
As  a  consequence,  the  kidney  reddens,  either  diffusely  or  shows 
hemorrhag;ic  dots  and  streaks,  correspondint>;  to  hemorrhaji;ic 
extravasations  into  the  glomeruli  and  tubules.  In  others,  again, 
the  degenerative  lesions,  fatty  metamorphosis,  seem  to  empha- 
size that  there  the  irritant  effects  a  primary  and  greater  injury 
of  the  fixed  tissue-cells.  In  these  cases  the  organ  appears  pale 
and  yellow.  Finally  an  oedematous  imbibition  in  some  forms, 
particularly  those  associated  with  general  oedema,  may  give  to 
the  kidney  an  almost  colorless,  but  moist,  appearance.  The 
kidney,  therefore,  show^s  here,  as  in  other  nephrites,  the  evidences 
which  point  toward  one  or  the  other  inflammatory'  attributes,  or 
both  may  become  combined  to  about  an  ecjual  degree.  In 
addition,  the  vascularity  must  l^e  influenced  by  the  inflammatory 
anatomical  changes  in  the  architecture  of  the  kidney.  Weigert 
went  so  far  as  to  hold  that  the  quantitative  differences  in  the 
blood-supply  and  inflammatory  engorgement  of  the  vessels 
accounted  fulh'  for  the  different  appearances  of  these  various 
forms  of  nephrites,  and  did  not  recognize  them  as  independent 
lesions.  Other  investigators  have  endeavored  to  establish  a 
definite  hemorrhagic  nephritis,  distinct  from  the  so-called  large 
pale  kidney.     That  there  is  no  essential  difference  between  these 


154  bright's  disease 

various  types  was  illustrated  very  forcibly  to  me  only  recently, 
when  I  found  a  typical  large  hemorrhagic  kidney  on  the  left  side, 
and  a  similarly  typical  large  pale  kidney  on  the  right  side,  of  a 
young  girl  who  died  of  a  slowly  progressing  nephritis.  It  ap- 
peared to  the  unknowing  as  if  these  two  perfect  examples  came 
from  different  individuals. 

It  has  been  claimed  by  some :  Edebohls  and  his  followers,  who 
advise  decapsulation  of  the  kidney  in  nephritis,  that  with  the 
attachment  of  the  capsule  to  the  parenchyma  collateral  circula- 
tion with  the  surrounding  structures  may  thus  be  established, 
but  extensive  experimental  observations  of  Thelemann,  von 
Cott,  and  Herxheimer  and  Hall,^^  and  others,  have  shown  con- 
clusively that  this  does  not  take  place,  and  after  decapsulation 
a  new,  much  thicker  capsule  is  soon  formed. 

Sooner  or  later  the  kidney  begins  to  experience  the  effect  of 
the  nephritic  process  on  the  whole  circulation.  I  will  not  discuss 
here  these  effects  on  the  heart  and  vessels,  which  belong  to  the 
last  chapter  of  these  lectures,  but  it  is  particularly  to  the  com- 
plicating pictures  which  venous  stasis  produces  in  such  late 
nephritis  that  I  wish  to  call  your  attention. 

Venous  stasis  in  the  kidneys  as  the  result  of  a  general  decline 
in  the  circulation  in  nephritis  may  occur  rather  early  in  the 
lesion,  before  secondary  atrophy  and  contraction  have  taken 
place,  or  late,  after  this  has  much  advanced.  In  either  case  it  is 
apt  to  considerably  modify  the  process,  and  to  lead  to  very 
complicated  anatomical  and  clinical  pictures.  If  the  circulation 
becomes  impaired  before  much  of  the  kidney  substance  has  been 
lost,  the  venous  engorgement  may  prevent  at  least  a  marked 
contraction  of  the  organ  altogether,  and  is  sometimes  responsible, 
I  believe,  for  a  remarkable  good  gross  preservation  in  the  size 
of  the  kidney.  The  distribution  of  the  blood-vessels  accounts  for 
the  fact  that  the  stasis  appears  first  and  is  best  marked  at  the 


DECJENERATIVE    AND    KXIDATIXK    NEPHRITIS  155 

junction  of  niocluUa  and  cortex.  Therefore,  the  Une  of  demarca- 
tion between  both  becomes  more  prominent.  Later,  the  meduHa 
shows  accentuation  of  its  vessels,  which  have  usually  been  much 
better  preserved  than  those  of  the  cortex,  and,  finally,  the  re- 
nin ininsi  channels  in  the  cortex  also  become  more  prominent. 
But  as  these,  as  well  as  the  glomeruli,  have  largely  been  lost  in 
the  inflammatory  process,  this  is  relatively  less  conspicuous. 
While,  then,  the  kidney  as  a  whole  feels  fuller,  is  engorged  with 
l:)lood,  and  denser,  this  occurs  relatively  at  the  expense  of  the 
cortex,  being  at  the  same  time  most  prominent  in  the  medulla. 
After  venous  stasis  has  existed  for  some  time,  it  leads  to  oedema 
and  hemorrhages  into  tubules. 

In  the  progress  of  the  lesion,  if  the  individual  does  not  suc- 
cumb, which  is  usual,  it  is  difficult  to  separate  the  effects  of  the 
stasis  from  those  of  the  nephritis,  as  the  quantitative  and  qualita- 
tive conditions  become  well  and  completely  interwoven.  Where 
the  blood  stagnation  is  marked  and  patchy  extravasations  occur, 
haemolysis  with  setting  free  of  blood  coloring-matter  and  precip- 
itation of  granular  pigment  in  such  affected  areas  takes  place. 
These  superadded  nutritive  disturbances  are  an  additional  cause 
for  patchy  atrophy  and  collapse  of  certain  parts,  while  others 
show  compensator}'  stretching  and  fullness. 

Clinically  such  advanced  cases  present  great  diagnostic 
obstacles,  on  account  of  the  necessarily  complicated  functions. 
These  cases  are  frequently  very  difficult  to  separate  from  long- 
continued  simple  stasis  with  failing  heart,  and  the  question  of 
determining  whether  we  have  primarily  a  heart  lesion  with  pro- 
gressive venous  stasis  or  primarily  a  nephritic  lesion,  which  has 
led  to  circulatory  disturbances  and  a  secondare'  venous  conges- 
tion, ma}'  be  impossible  to  solve.*     In  hospitals  which,  like  ours 

*  Professor  Senator  has  told  me  that  Traube  used  to  pay  particuhir  attention  to  the 
color  of  the  urine  in  such  cases.  In  venous  stasis  complicating  a  nephritis  the  color  re- 
mains pale  in  spite  of  lessened  quantity. 


156  bright's  disease 

(City  Hospital,  Xew  York),  receive  a  large  number  of  these  ad- 
vanced cases,  some  almost  moribund  on  arrival,  they  are,  as  you 
know,  more  or  less  naively  classed  as  cardiorenal,  which  leaves 
the  ultimate  diagnosis  to  the  pathologist.  While  this  is  not  a 
very  scientific  or  even  definite  diagnosis,  I  believe  that  such 
clinical  diagnoses,  although  practically  confessing  ignorance,  are 
better,  for  the  sake  of  reliable  statistics,  than  an  elaborate 
antemortem  anatomical  diagnosis,  which  cannot  be  controlled 
by  autopsy. 

Xow,  on  the  other  hand,  venous  stasis  may  not  occur  until 
late  in  the  disease,  and  after  secondary  contraction  has  well 
advanced,  ^^^lile  it  follows,  then,  the  general  course  I  indi- 
cated, it  necessarily  appears  much  more  irregular,  particularly  in 
the  cortex,  where  many  of  the  vascular  paths  have  been  either 
entirely  lost  or  obliterated,  and  distorted.  The  kidney  in  all 
these  cases  loses  much  of  its  pale  or  yellowish  color,  and  assumes 
a  darker,  cyanotic  appearance.  The  superficial  veins  appear 
prominent.  Here,  as  in  ordinary  stasis,  cyanosis  is  accentuated 
in  the  medulla,  and  must  not  be  confounded  with  hemorrhagic 
inflammation  or  inflammatorv^  exacerbation:  these  are  always 
more  prominent  in  the  cortex,  and  never  lead  to  dilatation  of  the 
larger  veins.     They  may,  however,  combine. 

Lastly,  to  sketch  the  functional  evidences  which  correspond 
to  the  morphological  changes  studied  in  this  lecture :  When  you 
consider  the  multitude  of  interacting,  constantly  varying  proc- 
esses which  are  here  involved,  and  the  time  over  which  these 
extend,  with  the  possi))le  complications,  I  think  you  will  appre- 
ciate that  similar  and  sometimes  very  complex  and  perplexing 
functional  corrolaries  will  go  with  them. 

As  long  as  the  processes  of  exudation  and  ck\generation  con- 
trol the  field,  the  amount  of  urine  is  diminished,  although  on 
account  of  the  less  brusque  process,  and  compensatory  action  of 


DKCENERATIVE    AND    KXIDATIVE    NEPHRITIS  \ ')7 

preserved  <!;loineriili,  it  is  somewhat  lar<i;er  in  quantity  than  in 
tlio  severe  (ie<i;enerative  and  exiuhitive  nephritis  investi<i;ated  in 
our  first  lecture  (usually  about  500  c.c.j.  For  the  same  reason 
blood  is  not  apt  to  be  present  in  larg;e  amounts,  and  the  urine 
appears  therefore  li,ij;hter  in  color,  particularly  as  the  normal 
colorin<i-matter  of  the  uiiiic  is  not  secreted  in  the  usual  quan- 
tity. Sei-uni-alhuniin  and  nucleo-albumin  are  present  in  consider- 
able (jiuintities,  the  former  from  0.5  to  2  per  cent.,  but  only  rarely 
more,  and  the  higher  percentages  reported  refer  to  those  of 
volume.  The  urine  is  very  rich  in  morphotic  elements,  and  as  the 
fatty  degenerative  feature  becomes  now  marked,  its  evidences  are 
abundant  in  the  microscopic  examination  of  the  sediment.  Fatty 
cells,  fatty  casts,  free  fat,  and  detritus,  above  all  others,  give  the 
lesion  a  characteristic  stamp  as  fatty  nephritis.  Where,  in  ad- 
dition, hemorrhages  occur,  the  blood  appears  in  the  urine,  but 
not  with  the  same  constancy  or  abundance  as  in  the  more  active 
lesions  previously  considered.  As  the  process  proceeds  and  the 
exudative  features  regress  gradually  to  the  background,  which 
allows  the  field  to  be  somewhat  cleared  and  superseded  by  the 
atroph}'  and  loss  of  the  tissue  with  productive  cicatrizing  changes, 
the  functions  show  corresponding  changes.  The  amount  of 
urine  rises ;  it  becomes  paler  and  clearer.  The  specific  gravity,  on 
the  other  hand,  is  lowered,  because  the  excretion  of  normal 
solids  is  not  improved;  the  amount  of  serum-albumin  and  mor- 
photic elements  is  diminished.  Finally,  when  the  process  of 
secondary  contraction  is  well  imder  way,  with  relatively  free 
paths,  and  the  glomeruli  largely  obliterated  and  non-function- 
ating, the  evidences  of  the  previous,  or  still  existing,  exudation 
are  usually  slight,  but  the  urine  surprisingly  large  in  quantity 
and  much  clearer,  almost  watery,  and  of  low  specific  gravity. 
This  increase  in  amount  of  urine  is  usually  coincident  with  a 
decided  diminution  in  the  general  oedema,  w^hich,  as  you  know. 


158  bright's  disease 

is  most  alwaj^s  ver}^  marked  during  the  early  stages  of  this 
nephritis,  and  which  we  will  more  fully  discuss  in  the  next 
lecture.  Albumin  and  morphotic  elements  diminish  corre- 
spondingly. One  must  be  careful  to  not  regard  this  frequently 
abrupt  and  perplexing  deceitful  change,  sometimes  associated 
with  a  feeling  of  relief  on  the  part  of  the  patient,  as  one  for  the 
better.  If  you  have  carefully  followed  what  I  presented  to  you 
here  to-day,  you  will  bring  these  evidences  in  proper  relation  to 
the  morphological  changes  incident  to  the  progress  of  the  disease, 
and  admit  no  repair  or  improvement.  In  reality,  we  are  dealing 
with  a  further  advance  in  the  loss  of  renal  substances  and  suffi- 
ciency, another  step  on  the  downward  road  to  the  fatal  termina- 
tion. The  last  is  frequently  hastened  by  an  exacerbation  of  the 
exudative  and  degenerative  processes.  Then  the  kidney  presents 
again,  as  much  as  it  is  able  under  the  changed  conditions,  these 
various  anatomical  and  functional  features.  But  it  is  possible 
that  an  individual  may  survive  one  or  even  more  of  these  exacer- 
bations. 

On  the  other  hand,  when  venous  stasis  becomes  manifest, 
this  is  responsible  for  other  superadded  functional  derangements. 

Here  also  the  urine  diminishes  again,  but,  contrary  to  the 
inflammatory  exacerbations,  does  not  lead  to  a  greater  albumin- 
uria than  formerly  existed  or  to  an  increase  in  morphotic  ele- 
ments. Later  a  relatively  small  admixture  of  blood-cells  becomes 
evident,  but  the  color  of  the  urine  remains  pale.  Recognition 
and  relation  of  this  complication  to  the  nephritic  process  may 
at  times  be  difficult. 

I  cannot  leave  this  discussion  without  at  least  mentioning  cer- 
tain related  kidney  changes  which  develop  late  in  primary  chronic 
venous  congestion,  and  not  as  the  result  of  nephritic  lesions.  You 
understand  that  frequently  in  diseases  of  the  heart  with  gradual 
failing    compensation,    long-continued    venous    congestion    will 


DEGENERATIVE    AND    EXUDATIVE    NEPHRITIS  159 

occur,  without  any  previ(ju.s  iuflainnuitioii  of  that  organ.  Here 
all  the  veins  become  enormously  and  pro<i;ressively  en<i;or<^ed, 
first  in  the  medulla,  later  in  the  cortex,  until  the  engorgement 
even  affects  glomeruli  and  arterial  vessels.  The  kidney  en- 
larges, becomes  extremely  rich  in  blood,  and  its  markings  ver}^ 
prominent.  Later,  it  assumes  a  more  diffuse,  cyanotic  appear- 
ance. As  the  result  of  the  mechanical  pressure  and  interference 
with  nutrition,  serum  will  transude  into  the  intertubular  tissue. 
The  kidney  appears,  therefore,  in  later  stages,  oedematous,  and 
the  interstitial  tissue  stretched,  homogeneous,  and  fibrillatecl,  es- 
pecially in  the  medulla,  while  the  tubules  are  relatively  com- 
pressed. Later,  blood  extravasations  occur  into  tubules,  and  sec- 
ondar\'  hsemolytic  changes,  with  setting  free  of  blood-pigment. 
The  latter  is  particularly  well  shown  in  the  glomeruli.  Xow,  as 
the  result  of  these  largely,  and  primarily  quantitative,  changes, 
atrophy  of  glomeruli  and  tubular  portions  occurs,  followed  ])y 
collapse  of  kidney  substance.  In  such  areas  cellular  lympho- 
cytic and  fibroblastic  masses  may  accumulate,  leading  to  more 
or  less  prominent  fibrous  tissue  growth.  As  a  result,  the  kid- 
ney shrinks  and  contracts  in  places,  and  the  surface  appears 
necessarily  more  coarsely  granular.  Allien  tubules  have  become 
cut  off,  cyst  formation  may  take  place  under  such  conditions, 
particularly  in  the  medulla.  This  kidney  has  been  described  as 
cyanotic  induration,  or  cyanotic  contracted  kidney,  and  is,  strictly 
speaking,  not  of  an  inflammatory^  type.  It  differs  from  the 
inflammatory  lesions  in  the  evidences  of  its  extreme  cyanosis, 
associated  with  general  oedematous  imbibition  and  massive 
prominence  of  the  larger  vascular  channels.  This  state  of  affairs 
never  reaches  equal  uniformity  of  distribution  or  the  same  di- 
mensions in  a  stasis  which  is  engrafted  upon  a  previous  nephritic 
lesion.  The  contraction  of  the  organ  in  the  cyanotic  induration, 
on  the  other  hand,  does  not  ever  acquire  the  proportions  often 


160  bright's  disease 

seen  in  the  inflammatory  processes,  but  the  kidney,  although 
coarsely  granular,  remains  large,  and  the  medullary  portion 
particularly  prominent,  bulbing,  and  the  cortex  never  excessively 
scarred.  Microscopically  characteristic  are  absence  of  marked 
degenerations,  or  evidences  of  old  or  recent  cellular  exudation. 
This  is  particularly  well  shown  in  the  glomeruli.  These,  although 
immenseh^  engorged  with  blood  and  some  escape  of  serum  into 
the  capsular  space,  with  occasional  adhesion  of  the  tuft  to  the 
same,  do  not  present  any  features  of  active  exudation,  nor  that 
general,  cicatricial,  and  hyaline  replacement  which  formed  so 
prominent  a  feature  of  the  inflammatory  conditions.  Dense  peri- 
giomerular  cellular  infiltrations  and  fibrous  tissue  growth  are  also 
absent,  but  whenever  this  forms,  it  grows  less  abundantly,  carries 
many  engorged  blood-channels  and  tubules  with  old  blood-pig- 
ment, and  throughout  has  a  characteristic,  pale,  oedematous 
appearance,  with  considerable  fibrillar  stretching.  Schmaus  and 
Horn  ^^  have  pointed  out  that  all  vessels,  arteries,  and  veins  are 
here  enormously  thickened. 

The  consideration  of  the  secondary  contracted  kidney  has 
alread}^  ushered  in  certain  new  problems,  which  I  have  either 
only  touched  upon,  or  held  over  for  the  consideration  of  the 
productive  types  of  nephritis,  to  which  we  will  next  devote  our 
attention. 


FIFTH  LECTURE* 

PKuDL'CTn'E      Xephritis.     (  "haxges     IX     Other     Viscera. 

(Edema 

(Je?itlemen: 

I  turn  to-day  to  the  last  chapter  of  nephritis,  to  the  considera- 
tion of  that  type  I  grouped  as  productive  nephritis,  and  which 
is  usually  spoken  of  as  chronic  interstitial  nephritis.  I  believe 
that  its  appearance,  at  least  grossly,  is  familiar  to  you.  We 
understand  by  it  an  extreme  atrophy  of  the  parenchyma,  with  an 
abundant  increase  in  fibrous  tissue.  Such  a  kidney  is  ver\' 
small:  the  smallest  kidneys  on  record  are  of  that  type.  The 
surface  is  extremely  irregular  in  the  uncomplicated  pure  cases, 
finely  granular,  with  delicate  cicatricial  contractions.  It  is 
either  reddish  in  color  or  pale,  sometimes  yellowish  pale.  On 
section  it  is  perfectly  evident  that  there  is  a  marked  diminution 
and  loss  of  kidney  substance,  particularly  in  the  cortex  most  of 
it  may  have  completely  disappeared.  In  cases  complicated  with 
arteriosclerotic  infarctions  deep  cicatrices  form  and  interchange 
with  the  finer  granulations.  The  normal  markings  are  usually 
entirely  obliterated.  Glomeruli  and  glomerular  rows  cannot 
often  be  made  out  at  all.  The  glomeruli  appear  more  frequently 
on  the  cut  surface,  in  the  form  of  small,  point-like,  pale  hyaline 
elevations.  On  the  other  hand,  in  places,  unusually  dilated, 
irregular  vascular  channels  run  through  the  cortex.  That,  as 
you  will  appreciate  in  a  moment,  is  produced  by  the  peculiar 
circulatory  modifications  which  prevail  in  this  kidney.  The 
intervening   tubular  parenchyma,   depending  on   the   vascular 

*  Delivered  on  Februaiy  22,  1909. 
12  161 


162  bright's  disease 

condition,  is  either  quite  pale  or  pinkish.  Smaher  and  larger 
cystS;  sometimes  acquiring  considerable  dimensions,  are  also 
commonty  distributed  through  the  cortex,  occasionally  at  the 
junction  of  medulla  and  cortex,  rarely  deeper  in  the  pyramids. 
As  a  rule,  this  line  of  demarcation  between  cortex  and  medulla 
is  poorly  defined,  except  in  cases  where  stasis  has  complicated, 
when  the  vessels  of  the  pyramids  are  unusually  prominent, 
and  radiate  well  into  the  cortical  remnants.  Sometimes  calcium 
or  urate  deposits  may  here  be  seen.  When  inflammatory  exacer- 
bations  have  supervened,  or  hastened  the  final  termination,  the 
whole  kidney  appears  more  diffusely  reddened  or  mottled.  In 
cases  of  far-advanced  contraction  the  pelvis  is  relatively  very 
large  and  very  fatty.  The  fat  extends  well  upward  between 
the  atrophied  pyramids.  Very  prominent  are  the  thickened 
arteries.  This  thickening  may  involve  only  the  smaller  ones, 
which,  on  section,  stand  out  prominent  and  gaping,  or  it  may  go 
so  far  as  to  affect  the  renal  artery  (Fig.  43). 

Two  questions  present  themselves  to  us  from  the  start : 
What  is  the  relation  of  this  form  of  nephritis  to  the  changes 
previously  discussed,  particularly  the  so-called  secondary  con- 
tracted kidney?  and,  secondly.  What  is  the  relation  of  that  ex- 
treme parenchymatous  loss  to  the  abundant  fibrous  tissue  pro- 
liferation? 

With  regard  to  the  first  question,  you  recall  that  Bright,  who 
took  a  uniform  view  of  the  whole  nephritic  process,  regarded  the 
contracted  kidney  as  the  last  stage  of  the  previous  two,  and  a 
similar  view  was  entertained  by  many  subsequent  investigators, 
notably  Henle,  Reinhardt,  Frerichs,  and  especially  Weigert. 
On  the  other  hand,  Christison,  while  acknowledging  this  to  some 
extent,  was  the  first  to  doubt  that  all  these  various  lesions  were 
stages  of  one  morbid  process.  This  gained  much  support  in 
England  in  the  works  of  Johnson,  Toynbee,  Simon,  and  Busk, 


Fig.  43. — Nephritis  produetiva.  Kidney  small,  weight  56  gms.,  from  a  woman  forty- 
six  years  old.  Surface  flattened  and  finely  granular,  pale.  Cortex  unifonnly  and  mark- 
edly narrowed,  so  that  the  better  preserved  medulla  appears  drawn  to  the  surface.  Normal 
markings  lost.  Whitish  areas  (mature  fibrous  tissue)  interchange  with  reddish  (\'ascular 
granulation  tissue)  or  yellowish-red  parts.  All  vessels  distinctly  thickened,  around  them 
frequently  white  fibrous  patches.  Pelvis  relatively  large.  Here  also  was  a  terminal 
fibrinous  pericarditis. 


I'KODrCTIVK  XKI'HUriMS.       VISCIOHAI.  CIIAXOKS.       (EDEMA      ](V.] 

with  wliich  we  hccaiiic  f;nnili:ir  in  tlic  first  lecture,  until  finally 
Samuel  Wilks  nnd  ( Irainj^er  Stewart  regarded  the  lar^e  white  and 
the  small  ,ii,rniiul;ir  kidneys  as  independent  affections,  and  Gull 
and  Sutton  (^ven  spoke  of  ^' arteriocapillary  fibrosis"  as  the 
cause  of  contracted  kidney.  Similar,  althou<ih  not  so  radical, 
were  the  ideas  of  Bartels  in  (jlermany,  who  definitely  separated 
the  so-called  primary  interstitial  nephritis  from  the  others;  in 
this  he  was  followed  by  Zie<;ler  and  his  pupils.  Senator,  you 
remember,  took  a  somewhat  reconciling-  view,  inasmuch  as  he 
holds  that  all  these  various  forms  may  be  definitely  related,  or, 
on  the  other  hand,  may  develop  independently,  and  also  result  as 
the  consequence  of  primary  arterial  changes.  Inflammatory 
exacerbation  in  them  may  occur  at  all  times.  Finally,  the  ten- 
dency on  the  part  of  some  modern  pathologists  and  clinicians — 
Marchand,  Lohlein,  Muller — seems  to  be  again  toward  the  older 
uniform  view  of  Bright.  It  has  been  pointed  out  by  them  that 
it  is  extremely  difficult,  if  possible  at  all,  to  separate  the  sec- 
ondary contracted  kidney  from  the  so-called  primar}^  interstitial 
nephritis,  and  that,  in  all  probability,  many  of  the  latter  are  the 
results  of  previous  exudative  inflammatory  conditions,  which 
have  remained  latent  or  progressed  exceedingly  slowly.  It  has 
been  claimed  by  some  that  the  secondary  contracted  kidney  is  an 
ansemic  one,  in  which,  even  after  much  loss  of  substance,  the 
degenerative  features  still  predominate,  and  that,  on  the  other 
hand,  the  primary  productive  nephritis  appears  as  the  typical 
small  red  kidney.^  Against  this,  however,  it  has  been  urged 
that  the  small  red  contracted  kidney  represents  only  a  later  stage 
of  the  large  hemorrhagic  degenerative  nephritis,-  which  has  a 
much  greater  tendency  to  contract,  on  accoiuit  of  l)etter  nutri- 
tion and,  therefore,  leads  to  abundant  connective-tissue  forma- 
tion. My  own  experience  in  the  matter  has  led  me  to  believe  that 
there  is  no  essential  anatomical  difference  in  any  of  the  changes 


164 

which  occur  in  this  type  of  productive  nephritis  from  those  which 
we  observed  in  the  other  forms  and  which  we  have  discussed  in 
detail.  On  the  other  hand,  it  cannot  be  denied  that  there  exists 
a  nephritis  the  development  of  which  differs  in  certain  points 
from  those  we  have  considered:  Inflammatory  features  are 
neither  so  intense  nor  so  general  and  diffusely  distributed  from 
the  start  as  in  the  types  of  nephritis  previously  discussed.  The 
process  presents  itself  as  a  gradually  advancing,  patchy  inflam- 
mation, leading  to  a  progressive  loss  of  circumscribed  areas 
of  kidney  substance,  while  other  parts  are  preserved  and 
their  functions  continued  and  compensated.  Gradually,  by 
changed  anatomical  conditions,  an  unusually  complicated  organ 
is  thus  formed,  whose  functions  show  marked  abnormali- 
ties. On  account  of  this  slow  progress  and  a  gradual  adapta- 
tion of  the  organism  to  these  conditions,  it  is  compatible  with  a 
longer  period  of  life.  Such  a  kidney,  however,  is  easily  vulner- 
able, and  may  experience  at  any  time  an  active  and  diffuse  in- 
flammatory exacerbation,  placing  it  in  the  category  of  the  types 
previously  studied. 

I  am,  therefore,  of  the  opinion  that  anatomically  no  particular 
feature  differentiates  any  of  the  contracted  kidneys  one  from  the 
other,  but  believe  that  the  mode  of  origin  and  development  may 
differ.  It  may  result,  first,  from  a  diffuse  inflammation  (the 
so-called  secondary  contracted  kidney),  or,  secondly,  very 
insidiously,  as  the  consequence  of  slowly  progressive  circum- 
scribed inflammatory  foci,  which  eliminate  kidney  substance  very 
slowly,  and,  therefore,  normal  functionating  parenchyma  is  re- 
tained for  a  considerable  time.  This  distinction  is  in  reality  a 
purely  relative  one,  and,  taken  with  the  time,  accounts  for  certain 
modifications  in  one  more  frequently  than  in  the  other.  In 
the  end  the  result  is  the  same,  but  may  be  considerably  hastened 
by    inflammatory    exacerbations.     From    this    standpoint    an 


PRODCCTIN  i:  NKI'UKITIS.       VISCKHAI.  (H  A.\(iP]S.       (EI)E.MA      165 

essential  difference  between  primary  and  secondary  contracted 
kidneys  does  not  exist,  except  in  the  localization  and  progress 
of  the  disease,  and  l)()tli  are  really  secondary'  to  previous  degener- 
ation and  exudation,  in  oiu^  witli  a  latent,  in  the  other  with  an 
active,  course. 

The  terms  primary  and  secondary,  contracted  and  interstitial 
nephritis  are  misleading,  therefore,  and  had  better  be  dropped 
altogether.  Anatomically,  we  should  speak  of  productive 
nephritis,  then,  when  the  exudative  and  degenerative  attributes 
are  less  prominent  and,  on  the  other  hand,  the  formation  of 
connective  tissue  ver\'  abundant.  It  is  evident,  therefore,  that 
the  causes  of  productive  nephritis  are  ver\'  numerous.  It  may 
either  result  from  a  previous  diffuse  exudative  degenerative 
nephritis  which  has  undergone  remission  and  cleared  in  certain 
areas,  so  that  conditions  for  a  patchy  progress  of  the  disease  are 
thus  created;  or  it  develops  very  insidiously,  usually  quite 
unknown  to  the  individual,  until  it  reaches  an  advanced  degree, 
and,  as  the  consequence  of  long-continued  intoxications — lead- 
poisoning,  etc.,  gout,  and  probably  metabolic  autointoxications. 
These  may  lead  directly  to  patchy,  irregular  injur}'  and  corre- 
sponding inflammatory  foci,  with  eventual  loss  of  kidney  sub- 
stance. 

In  the  description  of  this  productive  nephritis  we  may  safely 
disregard  all  the  various  changes  which  presented  themselves  to 
us  before,  and  devote  our  attention  mainly  to  those  characteristic 
features  which  appear  especially  accentuated  in  it. 

From  these  considerations  it  becomes  intelligible  that  the 
kidney  of  a  productive  nephritis  offers  the  greatest  variety  of 
pictures.  It  represents  really  a  combination  of  all  the  inflamma- 
tory features  which  we  previously  discussed.  Far-advanced 
fibrous  areas  with  hyaline,  contracted  glomeruli,  lost  or  dis- 
torted tubules,  may  change  abruptly  to  better  preserved  and 


166  bright's  disease 

even  health}'  kidney  parenchyma  in  the  state  of  compensatory 
hypertroph}'.  This,  again,  adjoins  patches  of  kidney  substance 
which  are  the  seat  of  recent  inflammator}^  degenerative  and  exu- 
dative foci.  The  latter  are  particularly  prominent  in  the  inter- 
tubular  tissue,  and  consist  of  lymphocytic  and  polyblastic  cells, 
which,  accompanied  by  fibroblastic  proliferation,  soon  lead  to 
considerable  stretching  and  thickening  of  the  intertubular  tissue, 
and  the  formation  of  wax}-,  mature,  fibrous  connective  tissue. 
Similar  lesions  prevail  around  and  within  the  glomeruli,  and  as 
we  have  become  fully  acquainted  with  them,  I  shall  not  discuss 
them  here  again.  On  account  of  the  slow  and  patchy  progress 
in  these  changes,  and  the  compensatory  possibilities,  the  nutri- 
tion of  the  organ  is,  as  a  rule,  in  much  better  state  than  in  the 
cases  of  brusque  and  general  nephritis,  where  inflammatory  de- 
tritus and  general  inflammatory^  swelling  seriously  block  the  nu- 
tritive channels.  As  a  consequence  the  production  of  new  cells 
and  fibrous  tissue  occurs  here  with  much  greater  abundance 
and  perfection  than  would  be  possible  under  these  conditions. 

These  ver\'  slow  developments  are  also  responsible  for  a 
complete  and  permanent  new  arrangement  of  the  components 
of  the  kidney.  I  consider  this  of  the  greatest  importance,  as  it 
accounts  in  no  small  degree  for  some  of  the  perplexing  functional 
deviations  which  are  ver\^  characteristic  and  constant.  These 
anatomical  changes  manifest  themselves  in  the  parenchyma  and 
in  the  vascularity  of  the  kidney.     Both  are  intimately  connected. 

In  the  tubules  two  changes  occur:  First,  a  complete  regenera- 
tion of  epithelium,  of  the  type  which  we  met  before — low,  smooth 
and  syncytial,  endothelial-like.  On  the  other  hand,  it  is  not 
uncommon  to  observe  the  formation  of  high,  cylindrical  epithe- 
lium within  old  tubules.  One  or  the  other  change  is  so  general 
that  we  may  safely  say  that  the  kidney  gradually  acquires  an 
entirely  foreign  epithelium,  being  morphologically  and  undoubt- 


PRODlCTnE  NEPHRITIS.       VISCERAL  CHANGES.      CEDEMA      167 

cdly  fuiictioiiall\'  distinct,  and  different  from  its  predecessor.  It 
is  most  conspicuous  in  the  convoluted  tubules.  Secondly,  the 
tubules  change  their  size,  shape,  and  course.  They  become 
more  tortuous,  are  frequently  of  an  adenomatous  type,  givinfi; 
rise,  therefore,  to  a  different  glandular  system  from  the  normal 
uriniferous  tubule. 

Of  greatest  importance  is  the  elimination  of  the  glomeruli,  as 
it  necessitates  and  accomplishes  an  entire  change  in  the  circula- 
tion of  the  kidne}'.  It  has  been  shown  by  Thoma'^  that,  where 
glomeruli  become  impermeable,  circulation  may  be  kept  up  by  a 
direct  union  of  afferent  and  efferent  vessels,  so  that  blood  reaches 
the  tubules  direct,  without  circulation  through  the  glomerulus. 
On  the  other  hand,  in  places  where  complete  loss  of  cortical 
substance  has  taken  place,  compensators^  dilated  channels  form 
in  the  cortex;  finally,  when  this  becomes  impossible  by  destruc- 
tion of  whole  cortical  capillary  systems,  medullary  vessels  are 
pressed  into  service.  Under  such  conditions,  the  blood  reaches 
the  medulla  directly,  avoiding  the  cortex  altogether.  This  is 
grossly  well  illustrated  by  the  appearance  of  abnormal  and  enor- 
mously dilated  vascular  channels  within  the  cortex  and  medulla. 

You  are  now  in  a  position  to  appreciate  that  in  the  well- 
developed  cases  of  this  type  of  nephritis  we  are  dealing  with 
kidneys  wliich  represent  entirely  reconstructed  organs.  The 
glomeruli  have  been  eliminated,  the  tubules  have  not  only 
changed  their  epithelium,  l3ut  also  their  course,  and  the  whole 
vascularity  of  the  organ  has  been  altered.  Xo  blood  circulates 
through  glomeruli,  and  much  avoids  the  cortex  altogether,  to 
proceed  directly  to  the  medulla.  As  the  consequence  of  these 
essential  interferences  with  the  structure  of  the  kidney,  far- 
reaching  functional  modifications  necessarih'  develop,  vastly 
different  from  anything  ever  ol^served  under  physiological  con- 
ditions.    You  readih'  luiderstand  how  difficult   it   will   be   to 


168  bright's  disease 

explain  the  functions  of  such  a  radically  changed  organ  on  the 
hand  of  simple  physiological  experience. 

But  before  sketching  these  pathological  functions  for  you,  we 
must  consider  some  other  morphological  features  of  this  nephritis. 

Of  great  frequency  are  cysts.  These  occur,  sometimes  few, 
at  other  times  in  great  number,  so  that  the  name  of  acquired 
cystic  kidney  has  been  given  to  such  cases.  The  size  of  the 
cysts  also  varies  greatly.  From  small,  point-like  prominences, 
they  ma}^  grow  to  grape-sized,  or  even  egg-sized,  globular  bodies, 
but  never  to  the  dimensions  of  the  congenital  cysts.  The  larger 
ones  contain  usually  a  thin,  water\^,  clear  fluid;  in  the  smaller 
ones  inspissated,  yellowish  or  greenish  material  is  not  infre- 
quently found.  These  latter  may,  as  Baum"*  has  shown,  calcify. 
The  origin  of  these  cysts  is  twofold.  In  the  first  place,  they 
represent  parts  of  isolated  uriniferous  tubules,  which,  having 
been  cut  off  by  the  sclerosing  inflammation,  undergo  cystic  dila- 
tation. It  is,  therefore,  held  by  some  that  the  cyst  fluid  repre- 
sents retained  urine.  But  the  different  nature  of  the  lining 
epithelium  of  such  cysts,  as  well  as  the  physical  and  chemical 
character  of  the  fluid,  makes  a  modified  secretion  probable.  On 
the  other  hand,  I  observed  a  good  many  years  ago — in  1895, 
while  working  in  Wiirzburg — that  some  of  these  cysts  are  dis- 
tinctly of  glomerular  origin.  This  can  be  directty  observed  in 
certain  smaller  ones,  where  location,  size,  and  arrangement  of  the 
wall  and  lining  epithelium  stamp  the  cyst  body  as  of  glomerular 
derivation.  Such  cystic  bodies  frequently  contain  what  I 
considered  remnants  of  the  glomerular  tuft.  I  held  the  opinion 
that  these  cysts  owed  their  origin  either  to  a  sclerosing  inflamma- 
tion or  to  a  stagnation  in  the  upper  parts  of  the  tubules.  Baum, 
however,  who  has  investigated  that  matter  later,  regards  them 
as  congenital,  and  as  an  incompletely  developed  glomerulus. 
But  his  arguments  are  not  entirety  convincing. 


I'l<()I)r("IM\K  XKIMIIM'I'IS.        \  IS('I<:HAI>  CIIAXCiES.       (EDEMA      169 

Of  tlio  greatest  iinpuiUincc  and  ititcrost  are  the  vascular 
changes.  The  arterial  chanji;es  in  nephritis,  like  those  occurring!; 
outside  of  it,  have  l)een  a  much-discussed  subject,  and  even  now 
th(M'e  is  no  exact  agreement  as  to  their  pathogenesis  and  relation 
to  the  nephritic  process.  We  may,  I  believe,  differentiate  here 
between  two  types  of  arterial  thickening  which  depend  partly 
upon  the  local  inflammatory  changes  and  partly  upon  the  results 
which  outside  influences  produce  in  the  arterial  system  of  the 
kidney.  Consequently  we  may  differentiate  between,  first,  an 
inflammatory  thickening  dependent  upon  the  local  long-con- 
tinued productive  inflammatory  processes.  This  plays  a  part 
primarily  in  the  adventitia  of  the  vessels.  Perivascular  infiltra- 
tions combine  with  fibroblastic  proliferations  and  lead  to  thick- 
ening of  the  adventitia.  Frequently,  however,  the  lesion  pro- 
gresses toward  the  lumen  of  the  vessel,  thereby  adding  an 
endarteritis  fibrosa  obliterans.  The  latter  is  particularly  the 
case  in  the  smaller  vessels,  and  may  possibly  also  be  traced  to 
a  direct  toxic  action  on  the  intima. 

Second,  the  vessels  may  show  a  process  of  arteriosclerosis  or 
atherosclerosis.  The  relationship  of  this  to  nephritis,  particu- 
larly, has  been  a  much-discussed  matter. 

We  owe  primarily  to  Jores,^  and  later  to  him  with  Prym,'  an 
extensive  study,  not  only  into  the  histology  of  the  lesion,  but 
also  into  the  gradual  development  of  the  arteriosclerotic  process, 
and  lately  Fahr^  has  added  a  study  with  particular  reference  to 
the  kidney.  Jores — and  this  has  been  corroborated  by  others — 
distinguishes  between  two  types  of  arteriosclerosis:  First,  hy- 
perplasia of  thick  elastic  lamellae,  which  are  derived  from  the 
internal  elastic  membrane.  This  is,  in  reality,  a  perfectly  phy- 
siological process  w^hich  may  be  traced  from  earh'  childhood. 
This  thick,  elastic,  internal  membrane  displays  a  great  tendency 
to  degeneration  and  fibrillar  disintegration,  associated  with  fatty 


170  bright's  disease 

degeneration  of  the  part.  Jores  regards  these  processes  as  the 
essential  feature  of  the  arteriosclerotic  process.  This  in  turn  is 
followed  by  connective-tissue  formation.  Secondly,  Jores  de- 
scribes, as  a  distinct  process,  a  simple  connective-tissue  prolifera- 
tion of  the  intima,  the  so-called  endarteritis  fibrosa.  He  looks 
upon  the  gradual  formation  of  the  elastic  lamellae  as  a  compen- 
satory process,  one  that  is  necessary  for  the  maintenance  of 
arterial  elasticity.  These  views  are  opposed  to  those  originally 
offered  by  Thoma,^  and  also  Ewald^^  and  Friedeman,^^  Rind- 
fleisch,  and  others,  who  look  upon  the  rise  in  blood-pressure  as  a 
cause  of  arteriosclerosis. 

Corroboration  and  extension  of  Jores'  views  have  recently 
been  advanced  by  Fahr.  He  not  only  traced  the  same  develop- 
ment of  the  process  from  early  childhood  to  old  age,  but  drew  at- 
tention to  the  fact  that  in  the  heart  appears  early  a  fine  elastic 
network,  which  during  later  life  may  take  on  considerable  dimen- 
sions. Fahr  brings  this  into  analogy  with  the  arteriosclerotic 
process.  On  the  other  hand,  he,  and  also  Roth,^^  emphasize  the 
fact  that  the  occurrence  of  arteriosclerosis  in  the  kidney  seems 
to  bear  no  relation  to  the  nephritic  process.  This  is  particularly 
corroborated  in  the  nephrites  of  the  young,  when,  in  spite  of  high 
blood-pressure,  little  or  no  hyperplasia  of  the  intima  occurs. 
Again,  this  may  be  marked  in  cases  when  no  productive  nephritis 
can  be  demonstrated. 

Based  on  his  observations,  Fahr  concludes  that  arterioscle- 
rosis of  the  renal  arteries  is  an  extremely  frequent  phenomenon. 
It  may  assume  considerable  dimensions  without  seriously  inter- 
fering with  the  kidney  structure.  On  the  other  hand,  it  may 
lead  to  conditions  which  in  time  produce  extensive  contractions 
of  the  organ.  The  opposite,  however, — arteriosclerosis  as 
results  of  a  nephritis — plays  only  a  very  subordinate  role. 
Fahr  believes,  therefore,  with  Marchand,  that  the  arteriosclerosis 


PRODUCTIVE  NEPHRITIS.       VISCERAL  CHANGES.       CEDEMA     171 


'''■*'. 


Fig.  44. — Marked  va:scular  thickening  and  narrowing  in  senile  and  arteriosclerotic  kidney. 

X  112. 


PRODTTTTVE    XEPIIRITTS.     VISCERA  I.    THAXriES.      (EDEMA      173 

of  renal  vessels  is  not  the  result  of  a  nephritis  nor  of  raised 
jjjeneral  blood-pressure,  but  the  expression  of  the  daih'  variations 
in  blood-pressure  in  a  vascular  org;an,  to  which  everv^  individual 
is  more  or  less  exposed,  dependino;  upon  occupation,  tempera- 
ment, and  mode  of  livin^r.  In  other  words,  a  wear  and  tear 
process. 

I  believe,  however,  that  it  cannot  be  denied  that  lono;-con- 
tinued  increased  resistance  in  the  kidney  as  the  result  of  ob- 
literation of  normal  vascular  paths  may  be  a  factor  in  producino; 
elastic  thickening-  of  renal  vessels.  This  view  was  particularly 
advocated  b}^  Rindfleisch.  A  combination  may,  therefore,  occur 
with  the  third  vascular  change,  which  may  be  observed  in  these 
kidneys,  which  consists  in  a  hypertrophy  of  all  the  coats,  partic- 
ularly of  the  media.  This  has  been  emphasized  by  Friede- 
man,^'^  who  separated  this  lesion  distinctly  from  the  arterio- 
sclerotic process,  although^  as  you  appreciate,  it  may  lead  to  or 
combine  with  it,  so  that  a  sharp  line  of  distinction  cannot  always 
be  drawn.  This  process  is  characterized  mainly  by  a  hyper- 
plasia of  the  muscle-fibers  of  the  media,  which  distinguishes  it 
from  granulomatous  arteritis,  endarteritis,  and  arteriosclerosis. 
In  them,  you  remember,  there  occurs  essential  loss  of  muscle 
tissue,  with  fibrous  or  elastic  tissue  replacement.  Indeed,  Adami 
looks  upon  this  as  the  essential  feature  of  arteriosclerosis.  The 
arterial  muscular  hypertrophy,  however,  has  been  traced  to  the 
same  causes  which  demand  excessive  muscular  contraction  else- 
where, and  which,  as  we  will  see  later,  find  marked  expression  in 
t  he  hypertrophy  of  the  heart .  But  here  again  the  local  conditions 
and  gradual  increasing  impermeability  of  the  vascular  paths  in 
the  progress  of  a  nephritis  may  also  play  a  role. 

Finally,  the  capillaries  show  infiammatoiy  endothelial  pro- 
liferation. This  necessarily  leads  to  thickening  of  their  walls, 
and  frequently  they  undergo  hyaline  transformation. 


174  bright's  disease 

We  see,  therefore,  that  the  thickening  of  the  vessels  which  is 
observed  during;  the  pro^Tess  of  a  nephritis  originates  either  from 
conditions  arising  within  or  outside  of  the  kidnej^  and  that,  as 
in  the  hypertrophy^  of  the  elastic  tissue  and  the  media,  both 
factors  may  be  active.  But  whatever  ma}^  be  their  origin,  they, 
in  turn,  are  apt  to  very  materially  influence  the  progress  of  the 
lesion.  This  occurs  particularly  in  the  arteriosclerotic  and 
the  inflammatory  endarterial  changes.  These  are  naturally  fol- 
lowed by  marked  diminution  in  the  caliber  of  the  vessel,  and,  in 
time,  lead  to  thrombosis  and  complete  obliteration  of  the  thus 
affected  vascular  channel  (Fig.  44).  The  result  of  such  an 
occlusion,  however,  has,  particularly  in  larger  vessels,  a  decidedty 
bad  effect,  as  it  is  necessarily  followed  by  infarction  of  the  area 
supplied  by  that  vessel.  That  part  undergoes,  therefore,  ne- 
crosis, is  entirely  lost,  and  heals  only  with  the  formation  of  a 
deep,  thick  scar  (Fig.  42).  Almost  all  advanced  cases  of  pro- 
ductive nephritis  show  these  evidences  of  previous  infarctions. 

This  leads  directty  to  the  consideration  of  the  so-called  ar- 
teriosclerotic and  senile  kidney,  which  is  usually  classified  as  the 
arteriosclerotic  t3^pe  of  productive  nephritis.  I  speak  of  it  as 
sclerosis  or  atrophia  renum,  because  its  inflammatory  nature 
appears  very  doubtful.  It  is  the  typical  senile  kidney,  and  on 
account  of  some  similarity  to  the  productive  types  of  nephritis, 
has  frequently  l^een  considered  as  identical  with  it.  There  are, 
nevertheless,  certain  features  which  justify  its  separation  from 
the  inflammatory  productive  nephrites. 

As  the  name  implies,  this  kidney  appears  during  later  life. 
No  definite  time  for  its  development  and  occurrence  can  be  given, 
any  more  than  an  exact  answer  to  the  question,  When  do  people 
age?  Indeed,  the  senile  kidney  is  dependent  upon  the  general 
process  of  aging  of  the  whole  individual,  and  more  particularly 
upon  the  conditions  of  its  circulatory  apparatus.     It  is,  therefore, 


# 


(^ 


Fig.  45. — Atrophia  senilis  arteriosclerotica.  Weight  50  gms.  From  a  woman,  seventy- 
four  years  old,  who  died  of  gangrene  of  gut  due  to  arteriosclerotic  thrombosis  of  arteria 
meseraica  superior.  Extreme  loss  of  w^hole  kidney  substance,  and  thickening  of  renal 
artery.  Idiopathic  hydronephrosis  extending  to  cystic  dilatation  of  the  medullary 
pyranaids. 


riionrcTiVE  Ni'^i'iiuri'is.     \  is('i;i{ai.  {'HA.\(iKs.     (kuema    175 

eminently  a  nutritive  disturbance,  into  the  production  of  which 
three  factors  enter:  First,  and  paramount,  the  condition  of  the 
blood-vessels  of  the  kidney;  second,  the  condition  of  the  <»;eneral 
circulation;  third,  certain  orj>;anic  cellular  changes  incident  to 
advanced  life. 

In  our  previous  discussion  about  the  arterial  changes  we 
learned  that  the  vessels  of  the  kidney  are  particularly  exposed  in 
an  unusual  de<2;ree  to  the  wear  and  tear  of  life.  Outside  of  the 
spleen,  there  is  perhaps  no  other  organ  which  is  so  constantly 
under  marked  variations  of  pressure,  tension,  and  rapidity  of 
blood-current.  All  the  arteries  in  advanced  life  show  evidences 
of  strain  in  the  form  of  the  various  processes  collectively  grouped 
under  the  term  of  arteriosclerosis  or  atherosclerosis,  but  for 
reasons  just  mentioned  it  reaches  in  the  kidney  more  general  and 
much  greater  dimensions.  With  Fahr  and  Marchand  we  may 
look  upon  renal  arteriosclerosis  as  physiological  for  advanced 
life ;  so  it  happens  that  a  characteristic,  rather  constant  feature 
of  the  senile  kidney,  recognizable  almost  at  first  sight,  is  pro- 
nounced thickening  and  narrowing  of  its  vessels. 

The  results  of  these,  and  possibly  still  other,  interferences  with 
the  nutrition  of  the  parts  show  themselves  in  parenchymatous 
atrophy  of  circumscribed  areas  of  the  kidney  substance.  The  glo- 
meruli and  the  connected  tubules  shrink,  become  hyaline,  and 
thus  the  involved  portion  collapses.  This  loss  of  substance  gives 
rise  to  the  formation  of  slowly  maturing  granulation  tissue,  rich 
in  engorged  blood-vessels,  usually  taking  origin  around  vessels; 
compensatory  and  sometimes  considerable  enlargement  of  the 
neighboring  structures  follows,  unless  they  also  have  become  in- 
volved in  a  similar  fate.  The  process,  which  commences  in  small 
patches,  may  finally  affect  a  considerable  portion  of  the  whole 
kidney  substance.  Remnants  of  tubules  have  become  buried 
within  the  increased  fibrous  tissue  as  adenomatous  loops  or  as 


176  bright's  disease 

cystic  papillaiy  bodies.  Small  hyaline  globules  may  be  the  only 
e%ddences  of  p^e^ious  glomeruli.  The  kidney,  as  a  whole,  dimin- 
ishes therefore  in  size  and  appears  irregularly  granular,  and,  de- 
pending upon  its  vascularity  and  the  presence  or  absence  of 
serous  imbibition,  which  I  wi]l  discuss  in  a  moment ^  is  either  red 
or  pale. 

This  state  of  affairs  has  almost  always  added  to  it  stasis. 
The  latter  depends  partly  upon  new  circulatory  conditions  within 
the  kidney,  partly  upon  the  gradual  weakening  of  the  general 
systemic  senile  circulation.  The  results  of  such  a  long-continued 
stasis  are  here  similar  to  those  which  we  met  before,  namely, 
dilatation  of  all  vascular  districts,  including  the  newly  formed 
capillaries  within  the  fibrous  tissue,  further  interference  with  the 
nutrition  of  the  parts  still  intact,  and  a  gradual  serous  imbibition 
of  the  tissues,  particular^  marked  in  the  medullar}^  portions. 

The  kidney,  therefore,  becomes  oedematous.  Its  general 
appearance  is  hazy;  the  markings  become  disturbed  and  less 
distinct.  It  is  for  these  reasons  that  kidneys  in  such  a  stage  are 
frequently,  but  wrongly,  spoken  of  as  nephrites,  and  not  in- 
frequently such  kidneys  are  regarded  as  an  infiammator}^ 
exacerbation  of  contracted  kidneys.  But,  as  j^ou  see  from  the 
short  description  of  its  pathogenesis,  it  represents  the  late  results 
of  a  long-continued  venous  congestion  superadded  on  non- 
inflammator}'  nutritive  disturl^ances. 

But  the  picture  may  become  still  more  complicated;  for  the 
arteriosclerotic  process  frequently  leads  to  complete  obstruction 
of  the  larger  vessels,  necessarily  followed  by  infarctions.  These 
infarcts,  which  occasionally  are  of  considerable  magnitude,  heal 
with  the  formation  of  deeply  retracting  scars.  It  is  herein  that 
this  kidne}'  differs  particularly  from  the  pure  types  of  productive 
nephritis,  and  it  gives  the  organ  a  coarsely  granular  surface. 
It  is  the  type  of  kidney  which  led  Gull  and  Sutton  to  their  ^'iews 
about  the  pathogenesis  of  nephritis. 


PRODUCTIVK  XKI'HHITIS.       VISCERAF.  TH  AXGES.      (EDEMA      177 

Finally,  I  should  mention  that  it  must  be  considered  doubtful 
whether  all  the  atrophic  changes  observed  in  the  senile  kidneys — 
and  that  applies  in  <;oneral  to  all  senile  organs — only  and 
absoluteh^  depend  upon  the  quantitative  influence  of  arterial 
chan<»;es.  No  doul:)t,  these  are  extremely  important.  There  are, 
however,  certain  evidences,  the  discussion  of  which  lies  outside  the 
scope  of  these  lectures,  which  seem  to  indicate  that  senile  atrophy 
of  cells  cannot  be  entirely  ascribed  to  the  changes  within  the  cir- 
culatory apparatus,  but  include  certain  other  qualities  inherent 
to  cell  life.  Indeed,  we  observe  some  senile  kidneys  without 
much  arteriosclerotic  coarse  contraction,  but  a  rather  uniform, 
simple  loss  of  secreting  substance,  the  surface  remaining  smooth. 

A  characteristic  feature  of  this  type  of  kidney,  and  already 
mentioned  in  my  second  lecture  on  the  theories  of  urinary  secre- 
tions, is  not  only  a  relatively,  but  absolutely,  large  pelvis,  w^hich 
sometimes  takes  on  such  dimensions  and  appears  so  dilated  that 
it  may  properly  be  spoken  of  as  hydronephrosis.  This  h^^lrone- 
phrosis  may  be  regarded  as  an  idiopathic  one,  for  the  reason  that 
it  cannot  be  attributed  to  an}'-  coarse  mechanical  interference 
with  the  outflow  of  the  urine,  but  appears  to  be  due  to  a  gradual 
decline  in  the  elasticity  of  the  contractile  elements  of  the  pelvis, 
and,  possibly,  of  the  ureter.  In  some  of  these  pelves  one 
observes  distinctly  a  disintegration  of  the  elastic  structures, 
which  appear  either  increased  or  markedly  diminished.  This 
point  has  considerable  practical  interest  and  bearing. 

It  is  evident  that  senile  kidney  will,  sooner  or  later  during 
life,  eliminate  enough  kidney  substance  to  produce  symptoms  of 
renal  insufficiency.  Here  pathological  and  clinical  classifications 
have  some  difficulty  in  harmonizing,  for  a  clinician  will  necessarily 
be  satisfied  to  group  such  cases  under  the  general  category  of 
nephritis,  while  the  pathological  anatomist  can  surely  not  be 
content  with  this. 

13 


178  brtght's  disease 

We  are  now  in  a  position  to  appreciate  that  not  every  granu- 
lar, cicatricial,  and  atrophic  kidney  is  a  nephritis.  It  may  result, 
as  we  saw  before,  from  a  long-continued  venous  cyanosis,  and, 
as  we  find  now,  from  nutritive  disturbances  incident  to  senile 
changes.  Even  the  anatomical  diagnosis  may  here  not  always 
be  easy,  and  must  be  made  with  thorough  appreciation  of  the 
factors  which  we  have  studied.  But  the  decision  of  this  point, 
particularly  in  relation  to  certain  cases  of  hypertrophy  of  the 
heart,  may  become  of  the  greatest  clinical  importance.  Great 
difficult}'  may  l^e  offered  in  cases  when  such  kidneys — as  you 
can  readily  imagine — become  the  seat  of  superadded  exudative 
and  degenerative  inflammatory  conditions. 

Let  us  return  to  the  subject  of  productive  nephritis.  We 
have  arrived  at  the  second  question  which  presented  itself  at 
the  start  of  this  chapter:  l\Tiat  is  the  relation  of  the  extreme 
parenchymatous  loss  to  the  abundant  fibrous  tissue  prolifera- 
tion? 

Here  we  step  once  more  on  very  disputed  ground.  You  will 
recall  from  the  first  lecture  that  there  are  two  entirely  opposed 
views  on  that  subject.  It  had  been  Weigert's  idea — and  in  this 
he  was  essentially  supported  by  Cohnheim  and  many  others — 
that  it  was  necessary  to  presuppose  a  parenchymatous  injury  in 
order  to  account  for  the  fibrous  tissue  growth.  He  regarded  this 
latter,  therefore,  as  strictly  compensatory.  An  entirely  different 
view,  however,  was  entertained  b}^  Bartels,  who  regarded  the 
hyperplasia  of  interstitial  tissue  as  the  primary  feature  of  the 
contracted  kidne}' ,  and  thus  created  the  conception  of  the  pri- 
mary interstitial  nephritis.  In  this  he  was  actively  supported  by 
Nauwerck,  who  held  that  epithelial  degeneration  13}^  no  means 
alwa3''s  preceded  the  interstitial  inflammatory  changes. 

Some,  like  Aschoff,  separate  entirely  the  connective-tissue 
formation  from  the  inflammatory  process,  and,  extending  the 


PRODUCTIVE  NEPHRITIS.       VISCERAL  CHANGES.      CEDEMA      179 

\'i('ws  of  Weig'ert,  look  upon  it  as  a  process  of  repaii-.  That  <i;roup 
of  investigators  is  therefore  unwilling-  to  speak  of  pi'oductive 
nephritis  at  all,  but  regards  all  the  various  lesions  of  proliferation 
and  production  of  new  tissue,  much  as  Virchow  did,  as  conse- 
quences of  the  inflammatory  degenerative  and  exudative  changes, 
wliich  form  no  part  of  the  inflammatory  phenomena,  but  an 
evidence  of  healing,  Aschoff  discards  the  terms  of  chronic 
nephritis  and  productive  nephritis,  therefore,  and  speaks  of 
nephropathia  chronica  inflammatoria.  By  this  he  means  a  long- 
continued  disease  of  the  kidney,  originating  on  an  inflammatory 
basis,  but  having  reached  stages  of  repair  in  various  types  of 
cicatrization.  He  recognizes  this  lesion  in  three  stages:  first, 
insufficiency;  second,  compensation;  and  third,  decompensa- 
tion. 

Now,  it  is  certainly  true  that  many  of  the  so-called  "  chronic 
interstitial  inflammations,"  representing  an  increase  of  fibrous 
tissue  at  the  expense  of  parenchyma,  are  not  inflammatory  at  all. 
What  is,  for  instance,  frequently  referred  to  as  chronic  interstitial 
myocarditis  is  generally  scar  formation  as  the  result  of  infarc- 
tions. Similar  illustrations  may  be  found  in  other  organs,  and  I 
have  already  insisted  before  you  that  in  the  cyanotic  induration, 
and  in  the  senile  and  arteriosclerotic  kidney,  we  are  dealing  with 
nutritive  disturbances  which  are  absolutely  unrelated  to,  and 
therefore  to  be  separated  from,  the  inflammatory^  conditions  of 
that  organ. 

However,  it  is  very  doul:>tful  whether  the  proliferation  of  cells 
and  formation  of  new  tissue,  which  is  characteristic  of  certain 
inflammations  and  with  w^hich  we  are  dealing  in  the  question  of 
.productive  inflammations,  can  property  be  regarded  only  as 
evidences  of  repair,  or  as  a  pure  healing  process.  There  are  some 
points  which  differentiate  them  from  the  previously  mentioned 
fibrous  iiTowth  which  results  from  nutritive  disturbances: 


180  bright's  disease 

First :  The  changes  in  the  interstitial  tissue  in  inflammator}^ 
processes  are  characterized  by  an  active  participation  of  compo- 
nent parts  of  this  tissue  in  the  defense  against  the  inflammatory 
irritant.  The  changes  thus  produced  differ,  therefore,  quantita- 
tively and  quahtatively  from  those  which  occur  during  the 
process  of  repair.  While,  therefore,  some  of  the  features  of 
repair  are  evident  in  the  inflammatory  interstitial  changes,  they 
have  others  so  closely  allied  and  acting  with  and  modifying  them, 
that  one  cannot  well  be  separated  from  the  other.  Further,  the 
close  interchange  between  interstitial  tissue,  parenchyma,  blood- 
vessels, and  lymphatics  lends,  as  we  have  learned,  certain 
qualitative  features  to  the  inflammatory  connective-tissue 
changes  which  go  far  beyond  those  found  in  reparative  processes. 

Second:  The  inflammatory  interstitial  proliferation  always 
grows  beyond  the  limits  of  repair.  This  important  point  had 
become  evident  even  to  Weigert,  who  therefore  introduced  the 
conception  of  hypercompensation,  later  used  by  Ehrlich  in  the 
elaboration  of  his  side-chain  theory.  The  process  of  repair, 
which  is  ushered  in  by  nutritive  tissue  disturbances,  remains 
distinctly  limited.  Into  its  formation  enters,  as  far  as  can  be 
seen,  only  the  removal  of  the  restraint  of  tissue  tension.  This 
once  reestablished,  the  proliferation  ends  and  matures  without 
affecting  in  the  slightest  degree  the  neighboring  intact,  or  even 
weakened,  tissue.  The  inflammatory  interstitial  proliferation, 
on  the  other  hand,  by  virtue  of  its  extensive  and  less  restrained 
growth,  b}^  blocking  the  paths  of  nutrition  and  absorption,  adds 
injur}^  instead  of  repair.  The  causes  for  this  must  undoubtedly 
be  sought  in  the  inflammatory  circulatory  conditions  and 
anatomical  rearrangement  of  the  parts,  more  complex  changes  of 
tissue  tension  than  in  simple  repair,  nutritive  changes,  and  con- 
tinuance of  certain  irritative  influences. 

Herein  lies  a  ver}^  decided  difference  between  pure  reparative 


I'RoDrcTn  i:  XP]PHRIT1S.       VISCERAL  fHAXGES.       CEDEMA      181 

and  inflammatory  tissue  ^rrowth,  and  one  which  justifies  us  in 
upholdinjz;  the  conception  of  productive  inflammation  as  distinct 
from  processes  of  repair. 

\()\v,  an  invosti<i;ation  into  the  problem  of  the  relation  of 
parenchymatous  loss  to  the  fibrous  tissue  formation  is  made 
extremely  difficult  by  the  complex  nature  of  these  changes,  and 
by  the  fact  that  it  is  rare  to  obtain  kidneys  in  such  stages  of 
incipient  nephritis  as  will  allow  definite  conclusions  on  that  point. 

It  seems,  however,  as  if  somewhat  intermediarv  and  more 
flexible  views  would  come  nearer  the  truth  than  any  one-sided 
and  rigid  idea :  Certain  forms  of  nephritis  are  associated  from 
the  start  with  progressive  parenchymatous  destruction.  It  ap- 
pears that  in  these  we  cannot  attribute  the  loss  of  parenchyma 
to  primar}'  proliferation  of  interstitial  tissue,  but  that  it  is  at  least 
concomitant,  and  by  its  loss  does  not  oppose  an  unrestrained 
connective-tissue  hyperplasia.  These  cases  would  conform  with 
Weigert's  views.  On  the  other  hand,  there  exist  types  of  neph- 
ritis which  originate  as  primarily  localized  perivascular  infiltra- 
tions. These  localized  areas,  however,  are  rapidly  followed,  pos- 
sibly by  virtue  of  their  existence,  possibly  by  extension  of  the 
inflammatory  irritant,  or  both,  by  nutritive  disturbances  of  the 
involved  parts.  Parenchymatous  destruction,  therefore,  ensues, 
and  inaugurates  the  possibility  of  further  extension  of  the  in- 
flammator\'  infiltrations  and  connective-tissue  growth.  With 
the  second  view  we  take,  as  you  may  see,  a  somewhat  reconcil- 
ing stand  between  extreme  ideas. 

Let  me  now  touch  upon  some  of  the  important  functional 
characteristics  of  productive  nephritis.  One  of  the  most  inter- 
esting is  the  strange  fact  that  throughout  the  course  of  this 
disease  the  urine  quantity  is  very  much  increased.  This  in- 
crease, although  not  reaching  such  high  figures  as  in  diabetes,  is 
nevertheless  considerable,  and,  curiously  enough,  persists  toward 


182  bright's  disease 

the  end.  That  is  its  most  perplexing  phenomenon.  No  matter 
whether  we  find  at  autopsy  almost  all  the  normal  kidney  sub- 
stance destroyed,  the  quantitative  excretion  of  the  watery 
elements  has  remained  high  to  exitus,  unless  circulatory  dis- 
turbances or  exacerbations  comphcate  the  terminal  picture. 
We  have  no  really  satisfactory  explanation  for  this  phenomenon. 
It  may,  of  course,  be  supposed  that,  particularly  at  the 
beginning  of  the  disease,  compensatory  hyperf unction  on  the 
part  of  the  preserved  kidney  portions  occurs;  but  how  does  it 
keep  up  as  the  kidney  substance  wastes  and  is  replaced  by  con- 
nective tissue?  It  is  here  particularly  that  we  must  look  for 
other  than  purely  physiological  reasons.  The  kidney  of  an 
advanced  productive  nephritis  is  really  not  comparable  to  the 
normal  organ. ^*  Not  only,  as  you  remember,  has  there  taken 
place  far-reaching  changes  in  the  vascular  supply  and  secreting 
channels,  but  the  epithelium  has,  as  you  also  recall,  changed  its 
type  entirely.  From  a  highly  differentiated,  specialized  form, 
it  has  either  become  cylindrical  or  more  frequently  descended 
further  to  an  endothelial,  syncytial-like  formation.  These 
atypical  forms  of  epithelium  receive  their  blood,  by  elimination 
of  most  glomeruli,  in  unmodified,  unconcentrated  form.  It  is 
evident  that  this  complete  reorganization  of  parts  must  be 
followed  by  far-reaching  effects.  In  the  same  way  we  may 
possibly  account  for  the  gradual  lessened  concentration  of  such 
urines,  which,  although  frequently  very  high  in  the  beginning, 
become  lower  in  specific  gravity,  until  toward  the  end  the  ex- 
cretion of  solids,  in  spite  of  an  abundance  of  urine  water,  is  far 
below  any  normal  figure. 

In  other  words,  the  late  manifestations  in  the  functional 
derangement  of  this  type  of  nephritis  seem  to  depend  on 
new  structural  forms  and  arrangement,  which  are  not  comparable 
to  the  physiological.     The  organ  is  a  new  functionating  unit. 


PRODUCTIVE  NEPHRITIS.       VISCERAL  CHAXGflS.       CEDEMA     183 

If  you  liax'c  followed  tlic  niorplioloj!;ical  c*han<ies  carefully, 
you  w  ill  icndilx'  sec  that  the  urino  in  the  pure  t3'pes  of  productive 
nephritis  must  l)c  poor  in  morphotic  elements  and  serum- 
albumin.  Destruction  of  kidney  substance  is  ver}'  slow,  cer- 
tainly never  intense,  and  wide-spread,  rapid  desquamation  of 
ej)itheliuin.  and  the  formation  of  much  inflammatory  detritus 
and  afti\e  diffuse  exudation  being  lacking.  A  moderate  num- 
ber of  hyaline,  occasional  granular  and  fatty  casts,  often  found 
only  after  (•onsidera))le  centrifuging,  and  occasional  leukocytes, 
are  therefore  the  only  elements  found.  Serum-albumin  exists 
only  in  traces,  except  where  the  lesion  is  complicated  by  amyloid 
degeneration. 

Herewith  we  have  finished  our  proposed  work — the  considera- 
tion of  the  pathological  anatomy  and  histology  of  Bright 's 
disease  as  far  as  the  kidneys  themselves  are  concerned.  From 
the  mass  of  evidence  and  known  facts,  it  has  been  my  endeavor 
to  select  the  most  important,  not  presenting  them  as  independent 
or  incoherent  descriptions  and  statements,  but  molding  them 
into  a  plastic  form  which  will  allow  you  to  form  visual  pictures 
and  relations  of  the  nephritic  processes. 

In  conclusion,  however.  I  must  touch  upon  some  features  of 
nephritis  which,  although  lying  outside  of  the  kidney,  are  really 
part  of  the  general  morphological  consideration  of  the  subject. 
First,  changes  in  some  other  viscera;  and,  secondly,  the  ques- 
tion of  oedema.  These  are  so  important  and  characteristic  that 
we  cannot  wtII  omit  them.  Of  the  changes  in  the  viscera  we 
immediately  recognize  those  of  the  heart  as  the  best  known  and 
very  important.  That  any  nephritis  which  extends  over  a 
longer  period  may  become  associated  with  a  hypertrophy  of  the 
heart  was  known  to  Bright,  and  so  overwhelming  has  been  the 
evidence  since  his  first  observations,  that  this  is  one  of  the  best 
accepted  complications  of  nephritis.     AMiile  the  carefully  talni- 


184  bright's  disease 

lated  observations  of  Bamberger  and  Traube  and  general  ex- 
perience emphasized  the  preponderance  of  the  hypertrophy  of  the 
left  ventricle,  it  is  really  only  xery  recently  that  indisputable 
evidence  has  been  furnished  about  the  manner  under  which  the 
heart  hypertrophies  in  nephritis.  By  careful  weighing,  accord- 
ing to  W.  Miiller's  method,  Romberg,  Hasenfeld,  and  Hirsch 
have  demonstrated  that  in  82  per  cent,  of  their  cases  all  cavities 
of  the  heart,  auricles  and  ventricles,  show  hypertrophy  of  their 
walls.  The  left  ventricle,  however,  presents  this  most  markedly. 
In  14  per  cent  only  the  left  ventricle  was  hypertrophied.^^ 
Hirsch  demonstrated  that  the  hypertrophy  of  auricles  and  the 
right  ventricle  follows  that  of  the  left  ventricle,  and  Passler  that 
the  right  side  only  hypertrophies  when  the  left  side  becomes 
insufficient . 

These  figures  are  accepted  by  Krehl  as  perfectly  conclusive. 
They  are,  however,  as  now  all  pathologists  and  clinicians  know^ 
open  to  some  variations. 

In  the  first  place,  it  is  well  settled  that  hypertrophy  of  the 
heart  occurs  only  in  those  cases  which  are  associated  with  an 
appreciable  rise  in  blood-pressure.  It  is,  therefore,  not  abso- 
lutely dependent  upon  or  associated  with  any  particular  kind 
of  nephritis.  While  it  is  most  constant  in  the  brusque  exudative 
t)'pes,  particularly  those  with  marked  vascular  injury,  as  in 
scarlet  fever,  and  in  the  productive  forms,  it  may,  nevertheless, 
be  absent  in  all  of  them  for  the  following  reasons :  The  factors 
leading  to  increased  blood-pressure  may  be  lacking;  or  the  or- 
ganism may  be  unable  to  respond  to  these  factors;  lastly,  a 
once  established  hypertrophy  may  give  way  to  later  atrophy. 
The  latter  two  features  are  important  to  remember,  and  have 
been  fully  demonstrated  by  our  own  records.  The  hyper- 
trophy then  occurs  and  persists  only  when  the  nutrition  of  the 
organ  is  kept  up  to  the  necessary  standard. 


PRODUCTIVE  NEPHRITIS.       VISCERAL  CHANGES.       CEDEMA     185 

Senator,'^  some  years  a^^o,  pointed  out  that  one  could  differ- 
entiate between  two  fomis  of  hypertrophy:  one  with  dilatation 
of  the  ventricle,  the  so-called  eccentric:  and  one  without  dilata- 
tion, simple  or  concentric.  He  concluded  from  his  obser\'ations 
the  occurrence  of  the  first  in  the  large,  de^cenerative.  exudative, 
fatty,  and  hemorrhagic  nephrites,  while  the  latter  was  the  rule 
in  the  small,  contracted,  productive  forms.  This  view  was  soon 
opposed  from  many  exceptions  by  Cohnheim  and  later  ob- 
servations, among  which  I  have  made  a  number  myself. 
These  demonstrated  the  dependence  of  eccentric  or  concentric 
hypertrophy  upon  the  general  nutrition  of  the  individual.  In 
the  degenerative  exudative  nephrites  with  much  oedema  and 
hydrops,  the  nutrition  of  the  indi^^dual  and  of  the  heart  muscle, 
particularly  toward  the  end.  suffers  severely:  naturally,  we  find 
at  autopsy  dilated  ventricles;  on  the  other  hand,  in  the  slowly 
progressing  uncomplicated  productive  nephritis,  the  nutrition 
usually  remains  \ery  good  till  toward  the  end.  Here  concentric 
hypertrophy  is  therefore  more  frequently  found.  An  absolute 
dependence  of  any  form  upon  a  particular  kidney  lesion  does 
therefore  not  seem  to  exist. ^' 

Xow.  how  is  this  hypertrophy  to  be  interpreted?  Bright 
held  to  two  possibilities :  Either  the  heart  is  directly  irritated  by 
an  abnormal  composition  of  the  blood,  or  this  affects  the  finer 
and  capillar\'  vessels,  thereby  augmenting  the  work  of  the  heart 
in  order  to  drive  blood  through  thus  affected  vascular  districts. 

The  immediate  successors  of  Bright  in  the  study  of  renal 
disease  did  not  further  our  knowledge  regarding  this  matter, 
until  the  work  of  Traube^^  gave  a  new  stimulus  to  it.  Traube 
showed  during  life  that  within  a  few  weeks  after  the  occurrence 
of  a  severe  nephritis  symptoms  appeared  which  pointed  toward 
increased  tension  in  the  aortic  s^'stem.  These  are  abnormal 
resistance  of  the  radials  and  the  apex-beat,  and  an  accentuated. 


186  bright's  disease 

high-sounding,  diastoHc  aortic  and  carotid  tone.  To  them  is 
added  soon  an  increase  in  the  heart  vokime,  and  Traube  demon- 
strated in  some  cases  hypertrophy  of  the  heart  in  as  short  a  time 
as  four  weeks  after  the  beginning  of  a  nephritis. 

In  this  way  he  concluded  a  causal  relation  between  nephritis 
and  hypertrophy  of  the  heart,  and  assumed  for  its  explanation 
the  following : 

First :  Inflammatory  lesions  of  the  kidney  cause,  by  presence 
of  an  exudate  or  by  loss  of  kidney  substance,  a  diminution  in  the 
amount  of  fluid  abstracted  from  the  aortic  system  for  the  pro- 
duction of  urine  water.  Second:  They  diminish  the  quality 
of  blood  which  in  a  given  time  flows  from  the  aortic  to  the  venous 
system. 

This  purely  mechanical  hypothesis  was  soon  attacked  for 
physiological  and  pathological  reasons.  It  was  demonstrated 
by  Cohnheim  and  Lichtheim  ^^  that  a  hydremic  plethora  has 
absolutely  no  influence  on  the  blood-pressure,  and  by  Ludwig 
and  his  pupils  that  even  tjdng  of  both  renal  arteries  had  no 
appreciable  effect  on  it.  Furthermore,  it  is  well  known  that, 
particularly  in  the  productive  nephrites,  the  amount  of  urine 
water  is  not  only  not  diminished,  but  actually  increased.  Never- 
theless, this  mechanical  theory  was  championed  by  Cohnheim 
in  modified  form,  largely  for  the  reason  that  experimentally  and 
clinically  left-sided  hypertrophy  follows  total  extirpation  of  one 
or  gradual  elimination  of  both  kidne^^s,  notably  exemplified  in 
cases  of  uncomplicated  hydronephrosis.  Lack  of  occurrence  of 
hypertrophy  under  these  conditions,  and  in  amyloid  kidney,  was 
attributed  by  Cohnheim  to  purely  nutritive  disturbances.  In 
order  to  meet  the  previously  mentioned  objections  to  Traube's 
theories,  Cohnheim  supposed  that  the  rise  in  pressure  was  due, 
first,  to  entrance  of  an  unchanged  amount  of  blood  into  the  kid- 
neys,  where   it   meets   increased   resistance,    and,    second,    an 


I'K()I)r('Tl\'K  NKI'HinTIS.       \'IS('I';H.\I,  CII.WCKS.       (KDHMA      1-^7 

almost  iioi'inal  (|ii;iiit  it  \-  of  urinous  substances,  which  determine, 
in  his  oj)inion,  the  (le<»;ree  of  contract il)ilit\-  of  tlie  smaller  renal 
vessels.  In  other  words,  (V)hnheim  believed  that  the  amount  of 
blood  cntcrin*;-  the  smaller  kidne}'  arteries,  whose  contractive 
state  is  determined  by  the  quantity  of  urinous  substances, 
remains  constant.  Beyond  these,  however,  it  meets  the  in- 
creased resistance  which  necessarily  leads  to  increase  in  "eneral 
arterial  tension. 

This  theory,  like  Traube's,  has  not  enjoyed  general  recogni- 
tion. Senator  -°  has  pointed  out  that  the  smaller  kidney  vessels 
are,  as  a  rule,  distinctly  diseased,  so  that  the  conception  ad- 
vanced by  Cohnheim  seems  unreasonable.  For  Krehl  -^  and 
others  it  is  impossible  to  understand  how  elimination  of  a 
relatively  small  area  of  circulation  should  be  followed  by  such 
a  permanent  rise  in  c;eneral  blood-pressure,  and  not  by  compen- 
satory dilatation  in  other  districts,  a  fact  which  is  the  rule  in 
other  conditions,  finally  there  is  no  direct  relation  between  the 
extent  of  hypertrophy  and  the  degree  of  kidney  contraction. 

Schmidt,--  who  differentiates  between  two  kinds  of  nephritis, 
glomerulonephritis  and  pure  parenchymatous  types,  in  which  I 
am  unable  to  follow  him,  believes  that  the  affection  of  the  glomer- 
uli is  of  greatest  importance  in  the  rise  in  tension  and  ultimate 
hypertrophy,  although  intensity  and  generality  of  the  glomerular 
lesions  do  not  seem  to  have  any  relation.  Schmidt  believes, 
therefore,  that  the  whole  is  a  reflex  process,  acting,  not  on  the 
heart  directly,  but  on  the  smaller  arteries.  But,  inasmuch  as  I 
have  never  seen  any  nephritis  without  glomerular  lesions,  I  can- 
not support  any  of  his  contentions.  But  granting  it,  one  cannot 
see  why  the  blood-pressure  is  so  extremely  high  in  late  stages  of 
productive  nephritis,  when  glomeruli  hiixe  largely  disappeared; 
and  why  much  lower  in  the  fatt}^  degenerative  type,  where  glom- 
eruli are  still  persistent  and  generally  diseased. 


188  bright's  disease 

By  far  the  largest  number  of  investigators  look  for  the  cause 
of  high  tension  and  hypertrophy  of  the  heart  outside  of  the  kid- 
ney. One  group  of  ideas  finds  the  explanation  in  changes  of  the 
arterial  system.  To  them,  rise  in  blood-pressure  and  hyper- 
trophy of  the  heart  is  not  dependent  upon,  but  associated  with, 
the  nephritis.  The  ideas  of  Gull  and  Sutton,  and  others,  on 
''arterio capillary  fibrosis,"  form  the  foundation  for  these  views. 
We  have  previously  studied  the  arterial  changes  in  the  kidney, 
and  those  of  the  other  arteries  outside  of  the  kidney  are  very 
similar.  Many,  as  we  saw,  are  not  the  cause  of,  but  actually 
dependent  on,  the  rise  of  blood-pressure  and  the  heart  hyper- 
trophy. Furthermore,  the  occurrence  of  arteriosclerosis  in 
nephritis  varies  so  much,  and  frequently  in  severe  cases  with 
much  hypertrophy  in  the  young  is  so  conspicuously  absent,  that 
we  cannot  bring  it  in  any  essential  relation  to  the  hypertrophy. 
Some  time  ago  the  question  of  splanchnic  arteriosclerosis  as 
cause  for  high  blood-pressure  was  much  discussed.  It  was 
thought  that,  although  the  larger  abdominal  vessels  might  not 
show  marked  lesions,  smaller  arteries  of  the  abdominal  organs 
in  spleen,  liver,  pancreas,  gut,  etc.,  presented  sufficiently  far- 
reaching  arterial  narrowing  to  account  for  rise  of  nephritic 
blood-pressure.  I  have  paid  some  attention  to  this  myself, 
but  have  been  unable  to  trace  any  satisfactory  relation  between 
splanchnic  arteriosclerosis  and  rise  in  blood-pressure. 

Ewald^'^  considered  that  an  increased  internal  friction  of  the 
blood  might  account  for  the  hypertrophy,  but  Hirsch  and  Beck"^ 
found  the  viscosity  of  the  blood  not  increased  in  nephritis. 

By  far  the  largest  number  of  investigators,  and  even  Bright, 
have  accepted  one  or  the  other  chemical  or  toxic  explanation  of 
rise  of  ))lood-pressure  with  hypertrophy  of  the  heart.  We  owe 
to  Senator  ^'-^  an  exceedingly  well-formulated  expression  of  this 
view,  and  the  ideas  of  other  investigators  along  these  lines  may 


PRODUCTIVE  NEPHRITIS.       VISCERAL  CHANGES.       CEDEMA      189 

well  be  reo;arded  as  modifications  of  Senator's  orio;inal  concep- 
tion. In  the  first  place,  he  holds  that  somewhat  different  factors 
are  potent  in  producino;  hypertrophy  of  the  heart  in  various 
forms  of  nephritis.  In  what  he  terms  "  parenchymatous 
nephritis."  and  what  we  call  degenerative  exudative  nephritis, 
the  kidney  and  the  whole  organism  are  exposed  to  an  irritant, 
which  therefore  acts  on  heart  and  blood-vessels  as  well  as  on 
kidneys,  and  produces  primarily  oedema.  The  latter  process 
removes  some  of  the  toxic  irritants  from  the  circulation.  If  the 
lesion  thus  ameliorates,  a  necessarily  somew^hat  weaker  but  per- 
sistent irritant  continues  a  vasocontraction,  followed  by  thicken- 
ing of  the  vessels.  Simultaneously,  this  irritant  acts  on  the 
heart  muscle.  The  heart  muscle  hypertrophies,  therefore,  for 
two  reasons:  First,  as  the  result  of  an  increased  resistance;  and, 
secondly,  as  the  direct  result  of  an  irritant.  These  are  the 
responsible  factors,  according  to  Senator,  in  w^hat  he  terms  the 
chronic  parenchymatous  and  secondary-  contracted  kidneys — 
conditions  which  we  called  degenerative  exudative  and  degener- 
ative productive  nephrites.  In  the  primary-  productive  neph- 
ritis, on  the  other  hand,  the  irritant,  although  constant,  is  never 
strong  enough  to  lead  to  hydrops  or  oedema,  but  produces  here 
also  contraction  of  smaller  arteries,  which  is  necessarily  foUowed 
by  hypertroph}',  particularly  of  the  left  ventricle.  Under  both 
conditions,  then,  a  similar  resulting  increased  pressure  in  the 
aortic  system  occurs :  These  ideas  were  actually  supported  by 
experimental  observations  which  showed  a  transient  rise  in 
blood-pressure  after  injection  of  urea,  although  Senator  himself 
is  inclined  to  attribute  an  even  greater  influence  to  the  other 
nitrogenous  waste-products. 

This  theorA'  is  vers'  ingenious,  particularly  as  it  accounts  not 
only  for  the  rise  in  blood-pressure  and  hypertrophy  of  the  heart. 
but  brings  these  at  once  in  a  relation  with  the  oedema  of  nephritis. 


190  bright's  disease 

As  I  told  you,  the  main  principles  of  this  toxic  theory  have  now 
been  generally  accepted.  Krehl's  idea,  which  is  somewhat 
simpler,  is  that  the  contraction  of  the  smaller  arteries  is  the  most 
important  factor,  and  that  this  is  not  to  be  regarded  as  a  spasm 
of  these  vessels,  but  rather  as  an  increased  tonicity  of  the  normal 
vascular  tone,  which  is  probably  under  the  influence  of  definite 
nervous  vascular  centers.  A  discussion  of  these  clinical  features 
of  high  blood-pressure  will  be  found  in  T.  C.  Janeway's  mono- 
graph on  the  subject. ^^ 

Against  these  ideas  it  was  again  urged  by  Cohnheim  that  they 
are  dealing  with  hypothetical  substances,  about  the  existence  and 
action  of  which  we  have  neither  proof  nor  any  knowledge ;  and, 
secondly,  that  in  the  early  stages  of  productive  nephritis,  when 
the  secretion  of  solids  and  urine  water  is  not  only  not  diminished, 
but  active^  increased,  the  arterial  tension  is  very  high  and 
the  circulatory  evidences  appear  frequently  before  any  of  the 
renal  lesions  become  manifest.  The  retention  of  urinary  pro- 
ducts, to  which  Senator  attributed  the  toxic  vascular  con- 
traction, must,  according  to  Cohnheim,  be  therefore  out  of  ques- 
tion. 

I,  too,  am  of  the  opinion  that  in  different  forms  of  nephrites 
different  factors  enter  into  the  production  of  rise  in  blood- 
pressure  hypertrophy  of  the  heart,  and  some  of  these  are  to  be 
found  outside  of,  and  some  within,  the  kidney.  In  the  first 
place,  it  appears  probable  that  in  the  early  stages  of  productive 
nephritis  a  toxic  factor  must  l^e  of  great  issue.  This,  as  evidence 
indicates,  cannot  be  a  retained  normal  urinary  product,  or 
products,  for  circulatory  changes  occur  at  an  early  date  when 
retention  of  urine  and  solids  is  not  only  not  diminished,  but 
increased.  It  is,  therefore,  more  probable  to  regard  it  as  an 
abnormal  either  infective  or  metabolic  poison,  which  increases, 
as  Krehl  suggests,  the  tonicity  of   all  blood-vessels  within  and 


I'RODl'CTIVK  XKIMIiirriS.        \IS('KI{A1.  ('HA.\(;KS.       (KI)IvMA      191 

outside  of  tlic  kidney  in  ixwinaiiciil  iasliioii,  Icnditiu'  to  I'isc  in 
hlood-prcssur-c,  liypcii  I'opliy  oi"  the  licaft,  and  a  <!;radual  waste 
of  kidney  substance.  The  whole  process  tlieii  increased  blood- 
pressure,  hypertroph>'  of  the  heart,'  and  nephritis — stands  in 
correlation  as  the  result  of  the  injury  of  a  foreign  invasion  and 
their  effort  to  eliminate  it  from  the  system.  Now,  as  the  kidney 
substance  wastes,  certain  new  complicating  factors  are  intro- 
duced on  the  part  of  the  entirely  changed  circulatory  conditions, 
and  we  may  regard  here,  although  modified  from  Traube  and 
Cohnheim,  a  certain  local  influence.  This  has  only  lately  been 
once  more  emphasized,  so  that  I  do  not  feel  justified  in  deny- 
ing it  all  importance,  as  some  would  have  it. 

We  have,  as  Cohnheim  held,  anatomical  observations  which 
indicate  that  elimination  of  the  circulation  of  the  kidney  is 
actual!}'  followed  by  hypertrophy  of  the  heart,  and  further 
experimental  work  has  again  turned  our  attention  to  the  ideas 
of  Traube  and  Cohnheim.  Thoma  found,  some  time  ago,  in 
his  experiments  on  the  circulation  in  contracted  kidne^^s,  a 
very  appreciable  resistance  within  the  kidney  district,  and 
Katzenstein  has  endeavored  to  prove  that  Cohnheim's  repty 
to  Ludwig's  objection  to  Traube's  theory  was  actually  correct. 
Katzenstein-^  showed  that,  while  Ludwig  and  his  pupils  were 
right  in  the  observation  that  tying  of  both  renal  arteries  outside 
of  the  kidneys,  or  at  the  hiius,  was  followed  by  no  rise,  but  even 
a  fall  in  blood-pressure,  things  differed  when  the  resistance  was 
introduced,  wdiile  the  renal  circulation  remained  in  connection 
with  the  aortic  one.  If  the  renal  circulation  was  resumed  after 
having  tied  the  renal  arter}'  for  a  long  enough  time  to  obtain 
thrombosis  in  the  vessels  of  the  kidney,  a  very  appreciable  rise 
occurred  and  lasted  several  hours.  These  experiments  corrobo- 
rated some  results  previously  recorded  l)v  Oscar  Israel,-'  who 
obtained  rise  in  blood-pressure  after  extirpation  of  both  kidneys 


192  bright's  disease 

in  fifteen  rabbits,  and  are  perhaps  less  objectionable,  because  an 
influence  of  urinary  substances  cannot  have  been  active. 

It  seems,  therefore,  that  we  cannot  entirely  dismiss  the  claims 
of  Traube  and  Cohnheim  that  certain  anatomical  and  experi- 
mental evidence  points  to  the  fact  that  resistance  within  the  renal 
circulation  may  have  an  effect  on  general  blood-pressure,  and, 
therefore,  if  not  the  origin  of  high  blood-pressure,  contributing 
toward  its  maintenance.* 

This  factor,  moreover,  seems  to  account  for  the  rise  in  blood- 
pressure  which  occurs  in  chronic  venous  congestion.  In  the 
various  forms  of  degenerative  and  exudative  nephrites,  however, 
it  is  possible  to  conceive  the  coexistence  of  toxic  and  local  condi- 
tions. In  the  later  stages  of  these  nephrites  the  waste  of  kidney 
substance,  the  new  arrangement  of  the  parts,  elimination  of 
glomeruli  and  other  vascular  channels  within  the  kidney,  may 
gradually  add  increasing  momentum  to  the  local  factor,  while 
the  occurrence  of  ursemic  manifestations,  with  sudden,  some- 
times tremendous,  rises  in  blood-pressure,  would  indicate  here 
also  the  persistence  of  the  toxic  influence,  which,  after  consid- 
erable accumulation,  suddenly  rises  to  exert  an  overwhelming 
effect. 

To  these  agents  must  finally  be  added,  in  some  cases  at  least, 
a  gradually  increasing  rigidity  of  all  blood-vessels,  which  is 
attributable  to  the  long-continued  increase  in  their  tonicity  and 
their  gradual  thickening. 

In  this  connection  a  few  words  about  the  relationship  of  the 
suprarenal  glands  to  blood-pressure  and  hypertrophy  of  the 
heart:  Recently  some  observers,^'*  particularly  among  the 
French,  have  claimed  that  in  long-continued  nephrites  with  high 

*  The  question  whether  this  is  due  to  a  reflex  or  mechanical  act  is  still  unsettled. 
Professor  Senator  told  mo  lately  that  in  recent  experiments  he  and  others  were  unable  to 
obtain  this  rise  in  blood-pressure  if  animals  were  deeply  narcotized.  This  would  argue,  of 
course,  against  a  mechanical  factor. 


PRODUCTIVP]  NKPHRITIS.       VISCERAL  CHANGES.       CEDEMA     193 

blood-pressure  a  hyperplasia  of  the  suprarenal  medulla  occurs, 
while  the  cortex  also  shows  nodular,  adenomatous  hypertrophy. 
This  is  broii<z;ht  in  relation  to  hi<^h  blood-pressure  as  an  expres- 
sion of  functional  hyperactivity  of  these  parts,  mainly  on  the 
stren<ith  of  the  physiolo<»;ical  experience  that  a  })lood-raisin^ 
principle  may  be  obtained  from  the  medulla  of  the  suprarenal 
gland,  while  a  detoxicatin<2;  power  is  ascribed  to  its  cortex.  It 
would  lead  me  here  too  far  to  <^o  into  an  elaborate  discussion  of 
the  whole  matter,  but  I  would  simply  mention  that  we  have 
been  unable  in  this  institute  to  corroborate  these  ideas,  and, 
indeed,  I  should,  from  our  experience,  conclude  that  general 
atrophy  of  the  cortex  was  a  very  prominent  phenomenon  in 
nephritis.  The  state  of  the  suprarenal  medulla  varies  so  decid- 
edly that  it  has  not  been  possible  for  us  to  bring  it  into  any  rela- 
tion to  the  nephritic  process. 

Of  great  importance  are  the  changes  in  the  serous  membranes, 
not  only  on  account  of  their  practical  interest,  but  because  they 
throw  some  light  on  the  genesis  of  oedema  and  hydrops,  which  we 
shall  lastly  have  to  consider. 

It  has  been  a  common  experience  that  nephritics  are  seriously 
threatened  with  inflammations  of  their  serous  membranes.  Of 
these,  it  is  particularly  the  pericardium;  then,  in  order  of  fre- 
quency, the  pleura,  the  peritoneum,  and  finally  the  meninges. 
So  frequent  is  the  combination  of  pericarditis  and  nephritis  in 
our  experience  that  when  we  find  recent  fibrinous  or  purulent 
pericarditis  at  autopsy,  we  immediately  expect  to  disclose  later  a 
nephritis.  The  same  holds  true  of  fibrinous  or  purulent  peri- 
tonitis, and  it  occasionally  happens  that  such  patients  are  oper- 
ated upon,  because  during  life  an  appendicitis  or  other  localized 
peritoneal  infection  is  suspected.  This  common  involvement  of 
the  serous  membranes  was,  as  you  will  recall,  known  even  to 
Bright  and  Christison.     It  is  usually  considered  that  the  cause 

14 


194  bright's  disease 

for  such  terminal  infections  lies  in  the  lessened  resistance  of  the 
individual  as  the  result  of  long-continued  nephritic  intoxications, 
but  if  we  examine  the  matter  carefully,  and  why  particularly  the 
serous  membranes  are  thus  so  easily  affected,  we  find  that  these 
have  almost  always  been  the  seat  of  previous  productive  and 
atrophic  inflammations.  It  is  one  of  the  commonest  autopsy 
findings  in  nephritis  to  see  the  serous  membranes  in  parts  thick- 
ened, either  diffuse,  giving  to  the  whole  a  white,  shiny,  pearly 
appearance,  or  only  circumscribed;  in  others  thin  and  wasted, 
deformed,  adherent.  Most  interesting  is  the  accompanying- 
productive  lymphangitis.  The  thickened,  partly  obliterated 
lymphatic  vessels  stand  out  very  prominently  in  the  form  of 
pale,  milky-white  streaks,  forming  an  irregular  network,  and, 
in  places,  accompanied  by  a  perilymphangitis,  become  confluent 
to  form  smaller  and  larger  patches. 

These  latter  lesions  are  usually  well  accentuated  and  easily 
observed  in  the  reflected  visceral  peritoneum,  but  can  also  be 
seen  in  pericardium,  meninges,  and  pleura.  From  this  experi- 
ence it  may  be  concluded  that  the  productive  inflammations  of 
all  serous  membranes,  which  often  become  associated  with  serous, 
fibrinous,  and  even  purulent  exudations,  are  the  result  and  ex- 
pression of  a  general  irritant  to  the  lymphatic  S3^stem  in  nephritis. 
It  leads  us  directly  to  the  causes  of  oedema  and  hydrops,  a  field 
which  has  for  years  been  one  of  the  most  fruitful  for  experimental 
pathology. 

For  a  full  discussion  of  the  early  works  and  thoughts  in  the 
matter  I  refer  you  to  the  masterly  presentation  and  criticisms 
of  Cohnheim  in  the  first  volume  of  his  lectures  on  general  Path- 
ology, Section  VII,  on  Hydraemia  and  Anhydraemia.  Recently 
the  matter  has  been  excellently  discussed  by  Meltzer  on  the 
vitalistic,  and  Starling  on  the  mechanical,  side.-'^  I  ^hall, 
therefore,  only  emphasize  certain  points. 


i'i{<)i)(  ("i'i\  i;  .\i:i'iiKi'iis.      \is('Ki{Ai.  (■ha.\(;ks.     (edema    195 

'\lw  oldest  conceptions,  now  (liscai(l('(l  as  essential  reasons 
lor  llic  j)i-o(luc1  ion  of  (edema  and  hydrops.  {)la('ed  the  liydraemic 
condition  of  tlic  hlood  as  forcMiiost  factor.  It  was  thouuht  that 
the  ,Li,ra(hial  with(h-awal  of  sernni-alhnniin  was  followed  ))y  a 
thinnini:- of  the  blood,  and  tliat  this  was  easily  permeable  through 
hlood-vessels.  This  idea,  however,  is  in  conflict  with  too  many 
facts  to  be  of  essential  consequence.  Later,  the  hydra^mia  was 
ascribed  to  water-retention — a  true  hydrsemic  plethora.  This 
latter  was  particularly  championed  by  Bartels,  who  especially 
emphasized  the  inverse  relation  of  diuresis,  oedema,  and  hydrops. 
However,  there  are  sufficient  evidences  to  deny  an  essential  role 
even  to  a  hydraemic  plethora,  for  the  reason  that,  as  Senator 
early  pointed  out,  oedema  appears  frequently  so  early  that  the 
existence  of  hydraemic  plethora  may  Ije  ruled  out  with  certaint}', 
and  that  diminution  in  the  amount  of  mine  does  not  even  lead 
to  a  hydraemic  plethora.  The  most  distiniiuished  objection 
came  here,  ai>:ain,  from  Cohnheim,  who,  with  Lichtheim,  pro- 
duced experimentally  in  animals  a  hydraemic  plethora  of  prob- 
ably .iireater  decree  than  is  ever  present  in  the  human  bein^i;. 
Such  experiments  were,  however,  never  followed  by  anasarca. 
But  if,  on  the  other  hand,  irritative  inflammatory  conditions  of 
the  skin  were  produced,  the  oedema  readily  followed.  For 
instance,  if  the  femoral  vein  of  a  healthy  do"-  was  tied,  no  oedema 
occurred,  yet  if  now  a  consideraljle  amount  of  a  sodium  chlorid 
solution  was  infused,  anasarca  resulted.  If,  further,  one  of  the 
hind  paws  of  a  dog  was  irritated  so  as  to  become  inflamed,  and 
cannulae  were  inserted  in  the  lymph-vessels  of  both  legs,  it  was 
observed,  after  injection  of  a  sufficient  quantity  of  a  solution  of 
NaCl  into  the  jugular  vein,  that  decidedly  more  lymph  dropped 
from  the  inflamed  extremity,  while  the  healthy  side  showed  no 
appreciable  change.  The  same  occurred  after  the  hydraemia 
was  continued  for  several  davs.     C  ohnheim's  conclusion  was. 


196  bright's  di^:pase 

therefore,  that  intact  vessels  through  which  a  normal  blood- 
stream flows  never  give  rise  to  oedema,  that  the  latter  is  the 
result  of  a  direct  injury  to,  or  nutritive  disturbances  in,  the 
vessel-walls.  These  views  found  further  corroboration  in  other 
observations.  I  may  only  recall  to  your  mind  that  certain  drugs, 
like  arsenic,  of  which  a  direct  injury  to  vessels  is  assumed,  lead 
to  the  production  of  oedema.  Magnus,^^  finally,  has  extended 
the  early  observations  of  Cohnheim  and  Lichtheim,  and  showed 
the  susceptibility  of  the  blood-vessels  to  a  number  of  substances, 
among  them  the  retained  normal  urinary  products. 

Of  greatest  interest  and  support  here  is  also  the  direct 
evidence  furnished  by  certain  forms  of  nephritis  in  which  we  can 
easily  recognize  marked  injury  to  vessels.  This,  as  you  recall, 
is  particularly  the  case  in  scarlatinal  nephritis.  In  scarlet  fever 
the  blood-vessels,  not  only  of  the  kidney  and  throughout  the 
whole  body,  but  of  the  skin,  are  in  decidedly  irritated  condition, 
and  oedema  is  one  of  the  most  prominent  symptoms.  Senator, 
therefore,  extending  these  views  of  Cohnheim,  speaks  of  the 
nephritic  hydrops  as  a  ''hydrops  irritativus."  We  could  easily 
quote  more  evidence,  particularly  of  an  experimental  nature, 
to  support  the  view  that  the  condition  of  the  blood-vessels — in 
other  words,  the  toxic  action  of  some  irritant  upon  them,  whereby 
their  permeability  is  increased — is  of  paramount  importance  in 
the  production  of  nephritic  oedema.^^  I  will  desist  from  doing 
it  because  evidence  is  here  so  strong  that  we  accept  it;  but  the 
question  remains  whether  it  is  the  all-important  and  only  factor 
in  this  matter.  This  possibility  must  be  denied.  For,  as  we 
know,  increased  transudation  is  by  no  means  identical  with 
fjedema.  In  order  to  obtain  the  latter  there  must  be  added  an 
interference  with  the  lymph-flow.  This,  however,  depends,  as 
you  recall  from  your  physiological  studies,  upon  the  pressure 
difference  in  the  capillary  and  lymphatic  systems.     The  pressure 


PRODUCTIVE  NEPHRITIS.       VISCERAL  CHANGES.       OEDEMA     197 

in  the  lyin};hatics  is  partly  dependent  upon  tlie  blood-pressure 
and,  as  Landerer'^-  has  shown,  the  tissue  tension  of  the  surround- 
ing structures.  Magnus  and  Krehl^^  have  pointed  out  that  these 
may  ven-  well  bo  involved  in  nephrites.  But,  unfortunately,  we 
have  as  yet  no  reliable  data  about  the  tissue  tension  in  nephritis. 
It  seems,  nevertheless,  very  possible  that  the  same  toxic  sub- 
stances which  injure  vessels,  injure  tissue  elasticity,  either  di- 
rectly or  by  high  osmotic  pressure  with  water  retention.  You 
recall  these  views  as  familiar. 

But  it  seems  that  the  changes  which  take  place  in  the  h'm- 
phatic  apparatus,  and  with  w^hich  I  made  you  acquainted  a  few 
moments  ago,  have  not  received  adequate  attention  in  their 
relation  to  the  production  of  oedema.  These  indicate  that  there 
must  also  l)e  a  decided  interference  with  lymph  resorption  and 
lymph  motion,  for  it  can  certainly  not  l^e  conceived  how  lym- 
phatics which  display  so  prominently  the  effect  of  irritative 
influence  on  the  form  of  productive  and  obliterative  lymphangi- 
tis and  perilymphangitis  can  continue  their  normal  functions; 
and.  as  a  matter  of  fact,  they  would  be  called  upon,  under  the 
previously  outlined  conditions,  to  do  increased  duty. 

I  am  inclined,  indeed,  to  regard  the  changes  in  lymphatics, 
for  which  we  have  anatomical  foundations,  as  very  essential 
for  the  production  of  any  pathological  transudate,  as  not  even 
Cohnheim  could  produce  oedema  after  injury  to  the  vessel-wall 
unless  the  l^lood  was  hydrsemic.  In  nephritis,  hoAvever,  it 
frequently  occurs  before  hydrsemia  has  developed.  The  lym- 
phatics have  usually  been  given  a  \er\^  subordinate  position  in 
the  relation  to  oedema,  mainly  on  the  ground  of  certain  evidence 
which  has  demonstrated  extensive  anastomosis  among  them. 
Obstruction  of  even  large  lymphatic  vessels  is,  therefore,  usually 
not  followed  ])y  any  accumulation  of  lymph  and  production  of 
oedema.     But  these  facts  are  hardly  applicable  to  the  question 


198  bright's  disease 

of  oedema  in  nephritis,  for  the  reason  that  we  are  not  only 
deahng  with  a  localized,  mechanical,  lymphatic  interference, 
which  may  l)e  adjusted  l3y  compensatory  action  of  healthy 
neighboring  lymphatics,  but  with  a  general  irritative  condition 
which  involves  all  the  tissue  lymphatics. 

If  we  finally  take  into  account  the  chemical  changes  which 
occur  during  certain  nephrites,  and  to  which  some  of  the  French 
investigators  have  attributed  much  influence,  we  can  readily  see 
how  they  may  add  to  the  ease  with  which  blood-serum  passes 
through  injured  vessel-walls.  It  has  been  demonstrated,  for 
instance,  that  retention  of  NaCl  has  at  times  considerable  in- 
fluence on  the  production  of  oedema;  but  this  has  been  found 
variable,  inconstant,  and  therefore  is  in  all  probability  not  an 
essential,  but  a  contributory,  factor.  To  the  same  contributory 
category'  would  belong  hydrsemia  and  venous  stasis. 

To  sum  up:  The  oedema  of  nephritis  depends  primarily  on 
an  output  of  serum  through  injured  capillary  districts,  which 
cannot  be  removed  on  account  of  similar  injury  to  the  lymphatics 
and  probably  the  surrounding  tissues.  Later  in  the  disease 
metabolic  and  mechanical  circulatory  disturbances  as  well  as 
retention  may  alter  the  composition  of  the  l^lood  and  the  vessel- 
walls  to  favor  further  the  passage  of  watery  elements  through 
the  capillar}^  sj'-stem. 

The  term  ''transudate"  is,  therefore,  not  strictly  correct  to 
apply  to  the  nephritic  oedema,  and  we  may  properly  foUow 
Senator's  precedent  and  speak  of  an  "  oedema  and  hydrops 
irritativus,"  which  at  once  brings  these  in  the  close  relation  to 
the  exudative  inflammations  of  serous  membranes  with  which, 
as  our  experience  taught  us,  they  so  frequently  complicate  and 
terminate. 

We  have  traced,  therefore,  nephritis,  increased  blood-pres- 
sure, hypertrophy  of  the  heart,  anasarca,  hydrops,  and  finally  the 


I'h'oDi  ("ii\  i:   \i:i'iiin'i'is.     nisciikal  cii  \.\(;ks.     (KI)i;.ma     199 

tci'iiiiiint  iii,i;  iii(l;iiiiiii;il  ions  of  1  lie  serous  iiiciiihiniics  to  a  genetic 
rcl.'it  ion. 

And  now  ;i  pnit  inii,  woi'd,  or,  hctler,  ji  .su<;'^ostion  from  t  lie 
palholoiiicnl  jiiuitomisl  to  you  :is  dinicinns.  on  llic  symptoms  of 
n<'j)li!ilis  ;in(l  IIhmi-  I'chition  to  the  nephritic;  process.  I  do  not 
mean  to  lire  you  l)y  a  detailed  discussion  of  these  symptoms, 
which  niusl  he  left  to  some  competent  chnical  exposition,  ])ut 
I  hoj)e  1  ha\c  impressed  upon  you  durin*;-  these  lectures  that  no 
nephritic  process  is  an  independent  lesion  of  the  kidne3^  For 
it  depends,  in  an  essential  degree,  upon  concomitant  and  corre- 
lated chan<i;es  outside  of  the  kidney.  This  is  so  much  the  case 
that  these  acquire  here  an  importance  almost  unparalleled  in 
the  diseases  of  other  origans.  We  saw  in  the  stud}"  of  the  anatom- 
ical features  tliat  we  must  sharply  separate  the  results  of  the 
inflammatory  changes  in  the  kidney  from  those  which  occur  as 
the  results  introduced  by  disturbances  from  outside.  Similarly, 
in  the  symptomatology  of  nephritis  you  will  find  that  the  com- 
plex clinical  pictures  of  the  various  types  may  be  separated  into 
two  great  groups  of  symptoms — the  renal  and  extrarenal.  The 
importance  of  those  in  individual  cases,  as  you  can  readih'  see, 
varies  constantly.  In  the  early  stages  of  slowly  progressing 
productive  nephrites,  for  instance,  the  extrarenal  symptoms  are 
of  much  greater  value  and  importance  than  the  renal,  for  the 
kidney  is  still  sufhcient,  and,  if  anything,  hyperfunctionates. 
Xot  until  much  later  occur  the  superadded  evidences  of  the 
serious  renal  involvement.  Vice  versa  in  some  of  the  rapidly 
developing  exudative  degenerative  types,  the  symptoms  of  the 
renal  affection  may  dominate  from  the  start,  and  later  become 
modified  1  )y  t  he  extrarenal  changes.  Herein  lies  a  great  difficulty 
in  the  study  of  renal  inflannnations.  And  if  this  offers,  as 
I  pointed  out  at  Ilu>  beginning  of  these  lectures,  great 
obstacles  on   tlu^   anatomical   side,   they   are   necessarily  much 


200  bright's  disease 

greater  on  the  clinical.  We  may  find  in  this  also  the  cause  for 
the  occasional  conflict  between  the  views  of  the  pathological 
anatomist  and  the  clinician.  The  latter  classifies  necessarih^ 
largely  according  to  certain  groups  of  symptoms  and  well- 
established  functional  disturbances,  which  represent  the  sum 
total  of  the  interferences  produced  b}"  a  disease  in  the  relation 
of  all  viscera  to  each  other.  The  former  classifies  the  changes 
in  one  organ  according  to  their  pathogenesis,  and  endeavors  to 
anatyze  them  in  more  or  less  abstract  independence. 

We  have  arrived  at  the  end.  Perhaps  my  presentation  of  the 
subject  has  seemed  very  old-fashioned  to  you.  It  perhaps  has 
been  discussed  too  much  for  your  tastes  in  well-trodden  paths,  or 
it  has  not  acquainted  you  wdth  new,  startling  ideas.  But,  after 
all,  it  ma}"  be  that  one  or  other  part  of  the  discussion  has  aroused 
your  o^Ti  thought  and  reason  to  go  further  than  what  was  here 
presented,  and  you  may  feel  more  encouraged  in  this  effort  if  I 
remind  you  of  a  remark  Goethe  once  made :  "  Alles  in  der  Welt 
ist  schon  einmal  gedacht  worden,  es  ist  nur  nothig  es  noch  einmal 
zu  denken." 


NOTES  AND  REFl^niENCES 

The  literature  on  Bright's  disease  is  so  enormous,  and  of  late  years  so 
much,  particularly  experimental,  work  has  accumulated,  that  it  has  been 
perf(H"tly  impossible  to  (!ven  mention  all  the  important  contributions  to  the 
various  j)liasos  of  the  subject.  Omissions  will,  therefore,  be  found  frequent, 
and  nmch  valuable  material  may  have  escaped  my  notice.  These  lectures 
were  not  intended  as  an  exhaustive  treatise  on  the  subject,  but  to  familiarize 
the  hearer,  and  now  the  reader,  with  the  fundamental  facts  and  to  give  him  a 
base  for  own  thought  and  research.  The  notes  and  references  are,  therefore, 
no  exhaustive  record  of  the  literature,  but  intended  to  supply  to  the  reader, 
not  only  corroboration  of  quotations,  but  to  open  a  particular  fiekl  which  he 
may  wish  to  pursue  further. 

FIRST  LECTURE 

1.  /Etii  medici  grffici  contracta3  ex  veteribus  medicina?  tetrabibli  sive  quater- 

nionis  tertii.     Lugduni  MDXLIX. 

Sermo  secundus  et  ex  ordine  decimus.     Cap.  xx.     De  hydrope  sive 

aqua  inter  cutem. 

Sermo  tertius  et  ex  ordine  unidecimus.     Cap.  xvi.     De  renum  in- 

fiammatione. 

Avicennse    arabum    medicorum   principis,    etc.     Venetiis    AIDCVIII 

Apud   Juntas.      Tom   i.      Fen   ii.     Doctrina  3.     De   significantibus 

coloris  urinse. 

2.  Before  Morgagni  similar  observations  were  recorded  by  Bonetus  in  his 

well-known  Sepulchretum  anatomicum,  ed.  Mangeti,  Lugduni  IMDCC, 
Lib.  iii,  sect,  xx,  observ.  xvi,  and  later  by  J.  Lieutand,  Historia  ana- 
tomico-medica,  etc.,  E.  Portal,  Paris,  1767,  i.  Portal,  Cours  anat. 
medicale.  Schenck,  Observat.  med.  rar.,  lib.  vii.  ]\lorgagni,  De 
sedibus  et  causis  morborum  per  anatomem  indagatis,  1761.  Epist. 
xxxviii,  xl,  and  xlii.  In  the  beginning  of  the  42d  epistle  the  history  of 
the  knight,  quoted  from  Valsalva,  will  be  found  ])articularly  interest- 
ing, not  only  from  the  pathological  standpoint,  but  as  a  contribution 
to  the  social  conditions  of  the  times. 

3.  Cotunii:   De  ischiade  nervosa  commentarius.     Vienna?,  1770,  p.  24. 
•4.  In  Rollo:   Diabetes  mellitus.     Chapter  vi,  London,  1798. 

5.  Observations  on  Dropsy,  which  Succeeds  Scarlet  Fever.  Transactions 
of  Society  for  the  Improvement  of  Medical  and  Chirurgical  Knowl- 
edge, vol.  iii. 

201 


202  bright's  disease 

6.  Brando :  An  Account  of  Some  Changes  from  Disease  in  the  Composition 

of  Human  Urine,  London,  1807.  Scudamore:  A  Treatise  on  the 
Nature  of  Gout,  London,  1823,  page  313. 

7.  Bright:  Reports  of  Medical  Cases,  i,  1827;  ii,  1831. 

8.  Cases  and  Observations  Illustrative  of  Renal  Disease,  Accompanied  with 

the  Secretion  of  Albuminous  Urine,  by  Dr.  Bright,  Guy's  Hospital 
Reports,  vol.  i,  MDCCCXXXVL  I  reproduce  here  his  excellent 
description  of  the  clinical  history  of  the  chsease  for  those  who  are  unable 
to  consult  the  original  on  pp.  339,  340,  and  341 : 

"A  child,  or  an  adult,  is  affected  with  scarlatina,  or  some  other 
acute  disease ;  or  had  indulged  in  the  intemperate  use  of  ardent  spirits 
for  a  series  of  months  or  years;  he  is  exposed  to  some  casual  cause  or 
habitual  source  of  suppressed  perspiration:  he  finds  the  secretion  of 
his  urine  greatly  increased,  or  he  discovers  that  it  is  tinged  with  blood; 
or,  without  having  made  any  such  observation,  he  awakes  in  the  morn- 
ing with  his  face  swollen,  or  his  ankles  puffy,  or  his  hands  oedematous. 
If  he  happen,  in  this  condition,  to  fall  under  the  care  of  a  practitioner 
who  suspects  the  nature  of  his  disease,  it  is  found  that  already  his 
urine  contains  a  notable  quantity  of  albumin.  His  pulse  is  full  and 
hard,  his  skin  dry,  he  has  often  headache,  and  sometimes  a  sense  of 
pain  or  weight  across  the  loins.  Under  treatment  more  or  less  active, 
or  sometimes  without  any  treatment,  the  more  obvious  and  distressing 
of  these  sjaiiptoms  disappear;  the  swelling,  whether  casual  or  constant, 
is  no  longer  observed ;  the  urine  ceases  to  evince  any  admixture  of  red 
particles;  and,  according  to  the  degree  of  importance  which  has  been 
attached  to  these  symptoms,  they  are  gradually  lost  sight  of,  or  are 
absolutely  forgotten.  Nevertheless,  from  time  to  time  the  counte- 
nance becomes  bloated;  the  skin  is  dry;  headaches  occur  with  unusual 
frequency;  or  the  calls  to  micturition  disturb  the  night's  repose. 
After  a  time,  the  healthy  color  of  the  countenance  fades;  a  sense  of 
weakness  or  pain  in  the  loins  increases;  headaches,  often  accompanied 
bj^  vomiting,  add  greatly  to  the  general  want  of  comfort;  and  a  sense 
of  lassitude,  of  weariness,  and  of  depression,  gradually  steal  over  the 
bodily  and  mental  frame.  Again  the  assistance  of  medicine  is  sought. 
If  the  nature  of  the  disease  is  suspected,  the  urine  is  carefully  tested; 
and  found,  in  almost  every  trial,  to  contain  albumin,  while  the  quan- 
tity of  urea  is  gradually  diminishing.  If,  in  the  attempt  to  give  relief 
to  the  oppression  of  the  system,  blood  is  drawn,  it  is  often  buffed,  or 
the  serum  is  milky  and  opaque;  and  nice  analysis  will  frequently 
detect,  a  great  deficiency  of  albumin,  and  sometimes  manifest  indica- 
tions of  the  presence  of  urea.  If  the  disease  is  not  suspected,  the  liver, 
the  stomach  or  the  brain  divide  the  care  of  the  practitioner,  sometimes 


NOTES    AM)    KKFKHKXCES  2().'> 

drawiiiK  liiiu  away  altof^cthcr  from  the  more  important  scat  of  diseaso. 
The  swelling  increases  and  decreases;  the  mind  grows  cheerful  or  is 
sad;  the  secretions  of  the  kidney  or  the  skin  are  augmented  or  dimin- 
ished, sometimes  in  alternate  ratio,  sometimes  without  apparent  re- 
lation. Again  the  patient  is  restored  to  tolerable  health;  again  he 
enters  on  his  active  duties:  Or  he  is,  perhaps,  less  fortunate; — the 
swelling  increases,  the  urine  becomes  scanty,  the  powers  of  life  seem  to 
yield,  the  lungs  become  a^dematous  and,  in  a  state  of  asphyxia  or 
coma,  he  sinks  into  the  grave;  or  a  sudden  effusion  of  serum  into  the 
glottis  closes  the  passages  of  the  air,  and  brings  on  a  more  sudden  dis- 
solution. Should  he,  however,  have  resumed  the  avocations  of  life, 
he  is  usually  subject  to  constant  recurrences  of  his  symptoms;  or 
again,  almost  dismissing  the  recollection  of  his  ailment,  he  is  suddenly 
seized  with  an  acute  attack  of  pericarditis,  or  with  a  still  more  acute 
attack  of  peritonitis,  which,  without  any  renewed  warning,  deprives 
him,  in  eight  and  forty  hours,  of  his  life.  Should  he  escape  this 
danger  likewise,  other  perils  await  him;  his  headaches  have  been 
observed  to  become  more  frequent;  his  stomach  more  deranged;  his 
vision  indistinct;  his  hearing  depraved;  he  is  suddenly  seized  with  a 
convulsive  fit,  and  becomes  blind.  He  struggles  through  the  attack; 
but  again  and  again  it  returns;  and  before  a  day  or  a  week  has  elapsed, 
worn  out  by  convulsions,  or  overwhelmed  by  coma,  the  painful  history 
of  his  disease  is  closed." 
9.  Christison:  Observations  on  the  Variety  of  Dropsy  which  Depends  upon 
Diseased  Kidneys,  Edinl^urgh  ^Medical  and  Surgical  Journal,  vol. 
xxxii,  1829.  And,  On  Granular  Degeneration  of  the  Kidney,  Edin- 
burgh, 1839. 

Osborne:    On  Dropsies  Connected  with  Suppressed  Perspiration  and 
Coagulable  Urine,  London,  1838;  and.  On  the  Nature  and  Treatment 
of  Dropsies;  Dublin  Journal  of  [Medical  and  Surgical  Sciences,  183-1. 
Gregory:  Edinburgh  Medical  and  Surgical  Journal,  xxxvi,  p.  315,  and 
xxxvii,  p.  54. 

10.  London  Medical  Gazette,  vii,  1831. 

11.  Dictionary  of  Practical  [Medicine;  under  Dropsy. 

12.  Dublin  Journal  of  Medical  Sciences,  1833,  16. 

13.  Urinary  Diseases  and  Their  Treatment,  London,  1838. 

14.  Rayer:  Traite  des  maladies  des  reins,  Paris,  1840. 

15.  Tissot:   De  I'hydropsie  causee  par  I'affection  granuleuse  des  reins,  Paris, 

1833. 

16.  Sabatier:  Considerations  et  observations  sur  I'liydropsies  symjitomatique 

d'une  lesion  speciale  des  reins.    Archive  generale  de  medecine.    Sec. 
ii. 


204  bright's  disease 

17.  Desir:    De  la  presence  de  I'albumine  dans  I'urine,  consideree  comme 

phenomene  et  comme  signe  dans  les  maladies.     Paris,  1835. 

18.  Genest:   Etat  actuel  des  connaissances  sur  la  maladie  des  reins  designee 

sous  les  denominations  de  maladie  de  Bright,  affection  granuleuse, 
nephrite  albumineuse.     Gaz.  med.  de  Paris,  1836,  p.  449. 

19.  M.  Solon:    De  I'albuminurie  ou  hydropsie  causee  par  une  maladie  des 

reins.     Paris,  1838. 

20.  Becquerel:   Semeiotique  des  urines,  ou  Traite  des  alterations  de  I'urine 

dans  les  maladies,  etc.     Paris,  1841. 

21.  In  Casper's  Wochenschrift,  38,  39,  40,  1839.     And,  Anatomische  und 

mikroskopische  Untersuchungen  zur  allgemeinen  und  speciellen 
Pathologic,  1838.  Later:  Abhandlungen  zur  Physiologic  und  Pathol- 
ogic, Jena,  1842. 

22.  Repcrtorium  fiir  Anatomic  und  Physiologic,  1837,  ii. 

23.  De  renibus  in  morbo  Brightii  degeneratis.     Dissert,  inaug.  Berol.     1839. 

24.  Zeitschrift  flir  rationelle  Mcdizin,  1841,  i,  p.  67;  ii,  p.  220,  and  Handbuch 

der  rationcllen  Pathologic,  ii,  1847,  p.  303  ff. 

25.  De  morbo  Brightii,  Erlangal,  1844. 

26.  Johnson:     Medico-Chirurgical    Transactions,    xxix,    xxx,    xxxii.     Also, 

The  Diseases  of  the  Kidney,  and  Lectures  on  Bright's  Disease. 

27.  Medico-Chirurgical  Transactions,  xxix,  p.  318. 

28.  Ibid.,  xxx. 

29.  Ibid.,  xxx. 

30.  Charite  Annalen,  i,  1850. 

31.  Frerichs:   Die  Bright'sche  Nieren  Krankheit,  etc.     Braunschweig,  1851. 

32.  Rockitansky:    Lehrbuch  der  pathologischen  Anatomic,  ii. 

33.  Ueber  parenchymatose   Entziindung,   iv,  p.   261.     (Classic.   Should  be 

read  by  everybody.) 

34.  Die    Bindesubstanz    der   Niere   im   gesunden    und    kranken   Zustande. 

Berhn,  1859. 

35.  Cohnheim's  work  on  inflammation  is  to  be  consulted  in  his  Vorlesungen 

liber  allgemeine  Pathologic;  on  the  kidneys  he  followed  mainly 
Wcigcrt's  views.     Ibid. 

36.  Traube's  views  are  presented  in:  Ueber  den  Zusammenhang  von  Herz  und 

Nicrenkrankheiten,  Berhn,  1856;  Deutsche  Khnik,  1859,  31-32; 
Allgemeine  med.  Centralzeitung,  1856,  65;   Deutsche  Klinik,  1863. 

37.  Klebs:  Lehrbuch  der  pathologische  Anatomic,  1876,  i,  144. 

38.  Nephritis  und  Albuminuric,  Bonn,  1881. 

39.  Die  Pathologic  und  Thcrapie  der  Nicrenkrankheiten,  1863  and  1894. 

40.  Verhandlungen  des  Congresses  fiir  innere    Mcdizin.     Erster   Congress, 

1882. 

41.  Guy's  Hospital  Reports,  viii,  1852,  2d  series. 


NOTES    AND    REFERENCES  205 

42.  A  Practical  Treatise  on  Bright's  Disease,  E<liiil)urji;li,  1S71. 

43.  Me(li{'o-(  'hirurgical  Transactions,  Iv,  1S72. 

44.  Voikniann's  Saninilung  kiinischer  X'ortriige,  1871,  35,  and  v.  Zienissen's 

Handbuch  der  spec.  Pathol.,  ix,  1,  1875  and  1877. 

45.  \'ircho\v's  Archiv,  Ixxiii,  1878.     Berliner  klinische  Wochenschrift,  1880, 

No.  29. 
4(3.  Die  Bright'sche  Nierenkrankheit  vom  pathologisch-anatomischen  Stand- 
punkt.     Voikniann's  Sammlung  kiinischer  Vortrage,  1879,  Xos.  162 
iind  163.     (An  exceedingly  important  work.) 

47.  I'eber    die    Ursachen    der    Nierenschumpfung.     Deutsches    Archiv    f. 

klinische  Medizin,  xxv,  1879,  p.  586. 

48.  Beitrage  zur  Kenntniss  des  Morbus  Brightii,  Ziegler's  Beitriige,  Jena, 

1886,  i. 

49.  Loc.  cit. 

50.  Die  Erkrankungen  der  Nieren.     In  Xothnagel's  series,  Wien.     A.  Holder. 

51.  Virchow's  Archiv,  xix,  1860. 

52.  Archiv  flir  Heilkunde,  1867. 

53.  Handbuch  der  pathologischen  Anatomie,  vol.  i,  1876. 

54.  Journal  of  Experimental  Medicine,  1898,  iii. 

55.  Lehrbuch  der  speciellen  pathologischen  Anatomie,  1893,  ii. 

56.  Loc.  cit.,  page  47. 

57.  Loc.  cit.,  page  190  ff. 

58.  Verhandlungen  der  deutschen  pathologischen  Gesellschaft,  Jahrgang  1905, 

p.  64. 

59.  Ueber  die  entziindlichen  Veranderungen  der  Glomeruli.     Arbeiten  aus 

dem  pathologischen  Listitut  zu  Leipzig,  1907,  monograph. 

60.  Studies  in  Pathological  Anatomy,  Acute  and  Chronic  Bright's  Disease. 

SECOND  LECTURE 

1.  Consult:    Schafer's  Histology,  Bohm  and  Davidoff's  Text-book  of  His- 

tology'-, and  Stohr's  Text-book  of  Histology.  Also  Landois  and  Ster- 
ling's Physiology,  where  histological  and  physiological  problems  are 
discussed.  Also  French's  Die  Bright'sche  Nierenkrankheit,  1851; 
Krehl,  Pathologische  Physiologie;  and  Oswald,  Lehrbuch  der  chem- 
ischen  Pathologie  (Harnabsonderung). 

2.  The  Development  of  the  Malpighian  Bodies  of  the  Kidney,  etc..  Journal 

of  Pathology  and  Bacteriology,  1900,  vi,  p.  459. 

3.  Consult  here  particularly  Starling  on  the  secretion  of  urine  in  Schafer's 

Text-book  on  Physiology,  vol.  i,  and  Hermann's  Lehrbuch  der 
Physiologie.  The  former,  particularly,  gives  a  readable  presenta- 
tion of  the  whole  subject. 

4.  Philosophical  Transactions.     London,  1842. 


206  bright's  disease 

5.  In    the    Wiener    Akademische    Sitzungsberichte.     Math.     nat.  Klasse, 

Hermann  in  Bel.  36  (1859),  p.  349;  Bd.  45  (1861),  p.  317. 

c.  Ludwig,  ibid.,  Bd.  48,  ii  (1883). 

c.  Ludwig,  Wagner's  Handworterbuch,  ii,  637. 

6.  Ribl)ert:    Virchow's  Archiv,  Bd.  xciii,  169.     After  removal  of  the  renal 

medulla  in  rabbits  Ribbert  observed  a  very  abundant  secretion  of 
thin  urine.  These  experiments  are  open  to  objection,  as  Munk  and 
Senator  point  out.  Loc.  cit.,  p.  23,  foot-note;  and,  further,  Boyd, 
Journal  of  Physiology,  vol.  xxviii,  1902.  The  later  evidence:  Hans 
Meyer,  Ueber  Diurese.  Sitzungsberichte  d.  Gesellschaft  zur  Befor- 
derung  der  gesammten  Naturwissenschaften.  Marburg,  1902,  p.  92 
ff.     Cushny,  Journal  of  Physiology,  1902,  vol.  xxvii. 

7.  Cited  after  Starhng,  Mechanism  of  the  Secretion  of  Urine,  in  Schafer's 

Text-book  of  Physiology,  vol.  i.  Pfeffer,  Osmotische  Untersuchungen, 
Leipzig,  1877.  Dreser,  Archiv  fiir  experimentelle  Pathologie  und 
Pharmakologie,  1892,  xxix,  307. 

8.  Verhandlungen  der  Deutschen  pathologischen  Gesellschaft.     Jahrgang 

1905.     Morbus  Brightii,  p.  64  ff. 

9.  Breslauer  arztliche  Zeitschrift,  1879,  22,  and  extensive  chscussion  in  Her- 

mann's Handbuch  der  Physiologie,  v.  i,  pp.  309. 

10.  Oertel:  Theories  of  Urinary  Secretion  from  the  Pathological  Standpoint. 

New  York  University  Bulletin  of  the  Medical  Sciences,  vol.  ii,  No.  2, 
April,  1902. 

11.  Sobieranski:   Archiv  fiir  exp.  Path.  u.  Pharm.,  xxxv,  144. 

12.  Senator:    Die  Albuminuric,  1882,  gives  a  full  discussion  of  this  subject 

and  further  references.  Also,  Verhandlungen  der  Berliner  Physiol. 
Gesellschaft,  Dec.  16,  1881,  in  Du  Bois  Reymond's  Archiv,  1881,  and 
Berliner  klin.  Wochenschrift,  1885. 

13.  Munk  and  Senator:  Zur  Kenntniss  der  Nierenfunktion,  etc.,  Virchow's 

Archiv,  114,  p.  1,  1888.  Senator,  Ueber  Transudation,  Virchow's 
Archiv,  111,  S.  219. 

14.  Fr.  Mliller:   Loc.  cit. 

15.  Loc.  cit. 

16.  Archiv  fiir  experimentelle  Pathologie  und  Pharmakologie,  vols,  xlviii  and  1. 

17.  Gottlielj  und  Magnus:   Ibid.,  vol.  45. 
IS.   Hofmeister's  Beitrage,  ii,  1902. 

19.  Ibid.,  ii,  1902. 

20.  Ue}K?r  Diabetes  insipidus  und  andere  Polyurien.     Deutsches  Archiv  fiir 

klinische  Medizin,  1905,  vol.  83,  p.  67  ff.     (Quotes  the  other  literature.) 

21.  Asher,  Troi)p  and  Michaud:  Zeitschrift  fiir  Biologie,  Bd.  45  u.  46. 

22.  Loc.  cit. 

23.  Zeitschrift  fiir  kliiiisciie  Mediziti,  33,  i,  1897;  34,  i,  1898. 


\()'i'i:s  AM)   |{i;ki:i{i;.\('Ks  1207 


THIRD  LECTURK 

(Icnvnil  reference  ivorks  un  nephritis  dud  dllied  suhjecLs: 
St'iuitor:     D'lv    iMkraiikunf^en    dcr    Xicrcii.     W'icii,    1902.     Alfred    Holder. 

((^uoti's  litcriiture  extensively.     \'ery  good  historical  introduction.) 
Kaut'mann:    Lehrhuch  der  specielleii  patlujlogischen  Anat(jmie,  Berlin,  1907. 

(Jei>r<j;  Reinier.      (Mxccilent  tor  reference  and  literature.) 
Zi(',a,ler:    Alliienieine  Patliolojiie  und  pat li()l<)<i;i.s('lie  .\natoniie,  Band  2,  Jena, 

liHX).     (aistav  Fischer.      (Literature.) 
Cohnheini:    \'orlesunf2;en  iiher  allii'enieine  Pathologic,  l>erliii,  1880.     August 

Hirschwald,  Zweitci-  P>aii(l. 
Ki-elil:    Pathologische  Physiologic,   Leipzig,  1907.     5th  Auflage.     F.   C  W. 

\'ogel.     (Particularly  for  the  functional  changes.) 
Orth:  Lehrhuch  der  speciellen  pathologischen  Anatomic,  II.  Band,  1.  Abtei- 

lung,  Berlin,  1893.     A.  Hirschwald.     (Literature.) 
Frerichs:   Die  Bright'sche  Nieren  Krankheit.     Braunschweig.     Vieweg,  18ol. 

(With  review  of  early  literature.) 
Aschoff :    Lehrhuch  der  pathologischen  Anatomic,  II.  Bd.      Jena,  Fischer, 

1909. 
Hoche  et  Briciuel:    Les  Lesions  du  Rein,  Paris,  1904.     (With  good  atlas.) 

1.  ]\IorlHis  Brightii.     Verhandlungen  der  deutschen  pathologischen  Gesell- 

schaft.     Jahrgang    1905,     p.     65.     Naturforscher    Versammlung    in 
Meran,  1905. 

2.  Die  ^'eranderungen  der  menschlichen   Xiere  nach   Sublimatvergiftung, 

etc.,  Ziegler's  Beitrage,  vol.  xlv,  p.  193. 

3.  lt)id..  p.  241. 

4.  Ibid.,  p.  200. 

5.  Cellular  Pathologic,  Berlin,  4.  Aufl.,  1871. 

6.  Die  Lchre  von  dcv  triiben  ^^chwellung,  Preisschrift,  Wurzl)urg,  1891. 

7.  Virchow's  Archiv,  cxlix,  p.  401. 

8.  Elemente  der  Pathologic,  3.  Aufl.,  1896. 

9.  \'orlesungen  iiber  allgemeine  Pathologic,  1882. 

10.  Allgemeine  Pathologic,  1889. 

11.  Lehrhuch  der  allgemeincn  Pathologic. 

12.  Lehrhuch  der  allgemeinen  pathologischen  Anatomic. 

13.  Lehri)uch  dcr  pathologischen  Anatomic. 

14.  Handl)uch  der  allgemeincn  Pathologic. 

15.  Mrchow's  Archiv,  cxxxv,  p.  470. 

16.  L'cbcr  triibe  SchwcUung,  Ziegler's  Bcitriige,  xxxiii.  1903. 

17.  Internationale  Zcitschrift  fiir  Anatomie  und  Physiologic,  1895. 


208  bright's  disease 

18.  Verhandlungen  der  deutschen  pathologischen  Gesellschaft,  1900. 

19.  Loc.  cit. 

20.  The  Principles  of  Pathology,  vol.  i,  1908. 

21.  Lehrbuch  d.  speciellen  pathologischen  Anatomie,  ii. 

22.  Specielle  pathologische  Anatomic. 

23.  Beer:  Loc.  cit. 

24.  Die    Bright'sche    Nierenkrankheit.     Volkmann's    Sammlung    klinischer 

Vortrage,  162-163.     1878-79,  pp.  144. 

25.  Archivio  per  le  szienze  mediche,  1883,  vi,  3.    Sulla  hypertrofia  compensa- 

toria  dei  reni ;  and  Neoformazione  dell'epitelio  dei  canaliculi  oriniferi 
della  malatta  di  Bright.     Ibid.,  1884,  viii. 

26.  Thorel:    Ueber  typische  und  Pseudoregeneration  bei  Niereninfarkten, 

Yirchow's  Archiv,  146,  1896. 

Rossle:     Storungen    der    Regeneration    von    Nierenepithelien.     Vir- 

chow's  Archiv,  170,  1902. 

Jatta:  Sulla  regenerazione  dell'epitelio  del  rene.     Archivio  per  scienze- 

mediche,  xxiii,  p.  323. 

Foa:   Ueber  Xiereninfarkte,  Ziegler's  Beitrage,  1889,  v. 

27.  Beitrage  zur  Anatomic  des  miliaren  Tuberkels.     II,  Ueber  Nierentuber- 

kulose.     Virchow's  Archiv,  1881,  83. 

28.  Ueber  Tuberkel  und  Tuberkulose,  Zeitschrift  fiir  klinische  Medizin,  ix-x. 

29.  Oertel,  Horst:   On  Epithelial  Proliferation  and  the  Formation  of  Epithe- 

lial Giant-cells  in  Nephritis.  Publications  of  the  Russell  Sage  In- 
stitute of  Pathology,  City  Hospital,  New  York,  i.     (Literature.) 

30.  Loc.  cit. 

31.  Beitrage  zur  Kenntniss  des  Morbus  Brightii,  Ziegler's  Beitrage,  i,  1886. 

32.  Die  Aetiologie  und   Genese   der  akuten  Nephritis.     Ziegler's  Beitrage, 

xl,  1892. 

33.  L'eber  Nephritis  scarlatinosa.     Fortschritt  der  Medizin,  i,  1883. 

34.  Nephritis  und  Albuminuric,  Bonn,  1881. 

35.  Loc.  cit. 

36.  Loc.  cit. 

37.  Inflammatory  Changes  in  the  Kidney,  etc..  Journal  of   Pathology  and 

Bacteriology,  July,  1904. 

38.  Zeitschrift  fiir  rationelle  Medizin,  Heft  i,  p.  62.     Also  described  by  Nasse 

in  Schmidt's  Jahrbiicher,  1843,  p.  356.  Further,  early  contributions 
by  Simon,  Beitrage  fiir  physiol.  und  pathol.  Chemie,  i,  p.  103,  and 
Scherer,  Chemische  und  mikroskopische  Untersuchungen,  Heidel- 
berg, 1843. 

39.  Roi'ida,  in  Moleschott's  Untersuchungen  zur  Naturlehre,  1872,  xl,  1. 

40.  Archiv  fiir  experimentelle  Pathologic  und  Pharmakologie,  vi,  p.  113. 

41.  Loc.  cit.  and  Die  normale  und  pathologische  Anatomie  und  Physiologic 


NOTES    AND    REFERENCES  209 

der  Xiere.  Bibliotheca  medica  C.  H.  and  Bildung  der  hyalineu  Z>  - 
linder.     Centralhlatt  f.  allR.  Path.,  iv,  1893. 

42.  Loc.  cit. 

43.  Ueber  triibe  Schwellung,  in  Ziegler's  Beitrage,  xxxiii,  193. 

44.  Granulabildung  bei  Nierenentziindung,  Ziegler's  Beitrage,  vii,  Supple- 

ment, 1905. 

45.  Israel:   Virchow's  Archiv,  cxxiii. 

Ernst:   Fibrin  in  hyalinen  Zylindern;   Ziegler's  Beitrage,  xiii,  1893. 

46.  Xatur  und  Entstehung  der  Nieren  Zylinder,  Centralblatt  fiir  allg.  Pathol., 

iv,  1893. 

47.  Loc.  cit. 

48.  Zeitschrift  fiir  klinische  Medizin,  i,  1879.     Centralblatt  fur  die  mediz. 

Wissenschaften,  1880.  Singer:  Zeitschrift  fiir  Heilkunde,  vi,  1885. 
Cohnheim  also  held  to  this  possibility. 

49.  Virchow's  Archiv,  Ixxvi. 

50.  Posner  (Virchow's  Archiv,  Ixxix)  looks  upon  most  casts  as  coagulated 

transuded  or  exuded  albumin,  and  derives  the  coagulating  ferment 
from  the  disintegration  of  the  leukocytes.  Similar  were  Weigert's 
views  (Virchow's  Arch.,  Ixxii,  p.  254). 

51.  Loc.  cit.,  Journal  of  Exp.  Medicine. 

52.  L'eber   Fettinfiltration  und  fettige   Degeneration  d.   Nieren,  Virchow's 

Archiv.  180.  1905. 

FOURTH  LECTURE 

1.  The  observations  of  Petrone  (1881)  and  Pisenti  (1884)  on  the  new  forma- 

tion of  glomeruli  and  new  tubules  have  generally  been  rejected  bj-- 
later  investigators. 

2.  Loc.  cit.,  p.  99. 

3.  Loc.  cit. 

4.  Zur    Entwicklungsgeschichte   des    Krebses     nebst    Bemerkungen   iiber 

Fettbildung  im  thierischen  Korper  und  pathologische  Resorption. 
Virchow's  Archiv,  i,  p.  94,  1847. 

5.  Pettenkofer  and  Voit,  in  Liebig's  Annalen,  Supp.  ii,  361,  Zeitschrift  fiir 

Biologic,  vi,  277  (1870);  vii,  433  (1871).  Bauer:  Zeitschrift  f. 
Biologic,  vii. 

6.  Die   Entstehung   von    Fett    aus    Eiweiss,    etc.      Ptiiiger's  Archiv,   77, 

1899. 

7.  Gibt  es  eine  fettige  Degeneration?    Verhandlungen  des  15ten  Kongresses 

fur  innere  Medizin,  1897.  And,  Ueber  Fettwandcrung  Verhandlungen 
des  13te  Kongresses  f.  inn.  Med.,  1895. 

8.  Ueber  Fettgehalt  des  Blutes  u.  einiger  Organc  des  Menschen,  Mrchow's 

Archiv.  174,  1903. 
15 


210  bright's  disease 

9.  Ueber  Fettansatz  im  Thierkorper,  Med.   Zentralblatt,.  8,  1882.     And, 
Pfliiger's  Archiv,  31,  11,  1883. 

10.  Ray,  MacDermott  and  Lusk,  American  Journal  of  Physiology,   1899, 

iii.  Lusk  and  Mandel,  Lactic  Acid  in  Intermediary  Metabolism, 
ibid.,  1906,  xvi.  Lusk,  Metabolism  in  Phosphorus-poisoning,  ibid., 
1907,  xix.  Lusk,  The  Elements  of  the  Science  of  Nutrition,  1906. 
Saunders. 

11.  Ueber  experimentell  erzeugte  Fettsynthese,  etc.,  Virchow's  Archiv,  174, 

1903. 

12.  Literature  on  autolysis:   Umber,  Die  Khnisch-pathologische  Bedeutung 

der  Autolyse,  Berliner  klinische  Wochenschrift,  1903,  xi,  185.  Opie, 
Journal  of  Exp.  Med.,  1905,  vii,  p.  316,  759.  Flexner,  Note  on  Au- 
tolysis in  Lobar  and  Unresolved  Pneumonia.  Transactions  of  As- 
sociation of  American  Physicians,  1903,  xviii,  1359.  Waldvogel, 
Autolyse  und  fettige  Degeneration,  Virchow's  Archiv,  1904,  175,  i. 
Phosphorvergiftung  und  Autolyse,  Deutsches  Archiv  f.  klin.  Medizin, 
1905,  82,  437.  F.  Miiller,  Pathologic  des  Stoffwechsels.  Levene,  P. 
A.:   Autolysis,  Harvey  Lectures,  N.  Y.,  1905-1906,  Lippincott  Co. 

13.  An  excellent  Discussion  in  Adami's  address  before  the  New  York  Harvey 

Society  on  Myehns,  etc.,  published  in  the  Harvey  Lectures  for  1906 
to  1907,  New  York,  Lippincott  Co.  For  the  chemistry  see  Hammer- 
sten,  Physiologische  Chemie,  translated  into  Enghsh  by  J.  Mandel. 
Also,  Hoppe-Seyler's  Physiologisch  und  pathologisch  chemische 
Analyse.  Aschoff,  Ziegler's  Beitrage,  Bd.  47,  i,  p.  7,  gives  the  most 
recent  and  extensive  discussion. 

14.  Oertel:  Beitrage  zur  Kenntniss  der  Ausscheidung  des  organischgebund- 

nen  Phosphors  im  Harn,  Zeitschrift  f.  physiol.  Chemie,  xxvl.  Keller, 
ibid.,  xxix.  Matthison,  Biochemical  Journal,  iv,  5,  6,  and  7.  Mandel 
and  Oertel,  N.  Y.  University  Bulletin  of  Medical  Sciences,  i,  p.  165, 
1901. 

15.  Symmers:  Journal  of  Pathology  and  Bacteriology,  vol.  x,  1905,  p.  159  ff. 

and  p.  427  ff. 

16.  See  Hammersten,  Lehrbuch  der  physiologischen  Chemie,  1907,  p.  338. 

17.  Ueber  Fettinfiltration,  etc.,  Virchow's  Archiv,  180,  1905.      Also,  Orgler, 

Ueber  das  Auftreten  von  Myelin  in  Zellen,  etc.,  Virchow's  Archiv,  167, 
1902. 

18.  See  Stoorck,  Uebor  Protagon  und  liber  die  grosse  weisse  Niere.     Sitzungs- 

berichte  der  K.  Akademie  der  Wissenschaften,  Math.-nat.  Klasse, 
Wien,  115,  1896.  Kaufman,  Specielle  pathologische  Anatomie, 
1907,  pp.  787-788. 

19.  See  Kraus,  Ueber  Fettdegeneration  und  Fettinfiltration.  Verhandlungen 


NOTES    AM)    REFERENCES  211 

der  Deutsclicn  pathologischon  Gesellschaft,  sechste  Tagung,  1904,  p. 
37  fT. 

20.  On  the  Large  White  or  Soapy  Kichu'V.     .iDunuil  of    Medical   Research, 

Boston,  XX,  p.  27. 

21.  Loe.  cit. 

22.  Loc.  cit. 

23.  Ueber  den  Lecithingehalt  des  Herzens  u.  der  Xieren,  etc.,  Arch.  f.  ex}). 

Pathologie  und  Pharmakologie,  .52,  178,  1905. 

24.  Lehrbuch  d.  chemische  Pathologie,  1907.      Has   a   review  of  the   sub- 

ject of  fat  degeneration  and  fat  infiltration. 

25.  Wichnian:  Die  Amj-loiderkrankung.     Beitrage  von  Ziegler,  xiii,   1893; 

and  Martland,  in  Medical  and  Surgical  Reports  of  New  York  City 
Hospital  for  1908.  Hueter,  Centralblatt  fiir  Pathologie,  Bd.  xix,  23, 
p.  961. 

26.  Herxheimer:    Hyaline    Degeneration  der  Glomeruli  der  Xiere,  Ziegler's 

Beitrage,  Bd.  45,  1909. 

27.  Histology  of   Liver  Tissue   Regeneration.     Journal   of  Patholog}'   and 

Bacteriology,  xiii,  p.  127. 

28.  Verhandlungen  der  deutschen  pathologischen  Gesellschaft,  1905.     Ueber 

Morbus  Brightii. 

29.  Herxheimer  and  Hall:   Ueber  die  Entkapselung  der  Xiere,   Virchow's 

Archiv,  179,  1905,  discuss  this  matter  fully  and  also  give  the  literature. 

30.  Ueber  den  Ausgang  der  cyanotischen  Induration  der  Xiere  in  Granular- 

atrophie.     "Wiesbaden,  1893. 

FIFTH  LECTURE 

1.  Fr.  Mliller:   Loc.  cit.,  p.  99. 

2.  Kaufmann:  Lehrbuch  der  pathologischen  Anatomic. 

3.  Zur  Kenntniss  der  Circulationstorungen  in  den  Nieren  bei  chronischer 

interstitieller  X^ephritis,  Virchow's  Archiv,  Bd.  71,  p.  42. 

4.  Ueber  die  punktformigen  Kalkkorperchen,  etc.,  Virchow's  Archiv,  Bd. 

162,  p.  85. 

5.  The  literature  on  arteriosclerosis  is  very  extensive.     The  following  will 

be  found  useful  for  reference:  Jores,  Wesen  und  Entwicklung  der 
Arteriosklerose,  Wiesbaden,  1903;  ^Marchand,  Ueber  Art eriosklerose, 
Kongress  fiir  innere  Medizin,  Leipzig,  1904.  A  somewhat  different 
stand  is  taken  by  Adami;  see  his  paper  in  the  October  number  of  the 
American  Journal  of  the  Medical  Sciences,  1909,  "The  X'ature  of  the 
Arteriosclerotic  Process,"  which  also  covers  Klotz's  work. 

6.  Loc.  cit.  and  Leber  die  Arteriosklerose  der  kleinen  Organarterien,  und 

ihre  Beziehungen  zur  Nephritis,  Virchow's  Archiv,  178.  Hypertrophie 
und  Arteriosklerose  der  Nierenarterien,  ibid.,  181. 


212  bright's  disease 

7.  Prym:  Ueber  die  Veranderungen  der  arteriellen  Gefasse  bei  interstitieller 

Nephritis,  Virchow's  Archiv,  Bd.  177. 

8.  Ueber  chronische   Nephritis  und    ihre    Beziehung  zur  Arteriosklerose, 

Virchow's  Archiv,  Bd.  195. 

9.  Thoma's  views  may  be  found  in  Virchow's  Archiv,  Bd.  93,  95,  104,  105, 

106.  Also,  Ueber  senile  Veranderungen  des  menschlichen  Korpers, 
Leipzig,  1884. 

10.  Ueber  die  Veranderungen   kleiner  Gefasse  bei    Morbus  Brightii,   etc., 

Virchow's  Archiv,  Bd.  71. 

11.  Ueber  die  Veranderungen  der  kleinen  Arterien  bei  Nierenerkrankungen, 

Virchow's  Archiv,  159,  1900.  And,  reply  to  Jores,  Virchow's  Archiv, 
Bd.  180. 

12.  Ueber  Schrumpfniere  ohne  Arteriosklerose.     Virchow's  Arch.,  180. 

13.  Loc.  cit. 

14.  Kretz  (Ueber  Lebercirrhose.     Wiener  klinische  Wochenschrift,  2,  1900.) 

Similarly,  has  shown  an  entirely  changed  regenerative  reconstruction 
in  the  architecture  of  the  liver  in  cirrhoses. 

15.  Consult    here    the    presentation    of    Krehl,    Pathologische    Physiologie, 

Leipzig,  1907,  pp.  33  ff.  (Literature.)  And,  Senator,  Die  Er- 
krankungen  der  Nieren,  p.  110  ff. 

16.  Virchow's  Archiv,  Ixxiii,  1878. 

17.  Senator  still  holds  these  views  on  the  ground  of  clinical  evidence,  which 

he  considers  here  stronger  and  more  conclusive  than  the  anatomical. 

18.  Ueber  den  Zusammenhang  von  Herz  und  Nierenkrankheiten,  Berlin, 

1856.  And,  Nachtragliche  Bemerkungen  dazu  in  Deutsche  Klinik, 
1859,  31  and  32.  An  excellent  modern  presentation  of  the  whole 
subject  of  blood-pressure  in  T.  C.  Janeway's  monograph,  ''  The 
Clinical  Study  of  Blood-pressure." 

19.  Cohnheim:  Allgemeine  Pathologic,  vol.  ii,  2te  Aufl.,  pp.  258  and  361. 

20.  Loc.  cit.,  1902,  p.  122. 

21.  Pathologische  Physiologie,  p.  38,  etc. 

22.  Verhandlungen  der  Deutschen  pathologischen  Gesellschaft,  1905.     (In 

the  general  discussion  on  Bright's  disease.) 

23.  Du  Bois  Reymond's  Archiv,  1877. 

24.  Hirsch  and  Beck:  Archiv  f.  kUnische  Medizin,  69,  503,  and  72,  560. 

Archiv  fiir  experimentelle  Pathol.,  etc.,  54.     (Cited  by  Krehl.) 

25.  Loc.  cit.,  p.  125.     Virchow's  Archiv,  Ixxiii,  1878. 

26.  Exporimentellcr  Beitrag  zur  Erkenntniss  der  bei  Nephritis  auftretenden 

Hypertrophic  des  linken  Herzens,  Virchow's  Archiv,  182,  p.  327. 

27.  Virchow's  Archiv,  86,  p.  295. 

28.  Consult  Pearce,  in  the  Journal  of   Experimental  Medicine,  x,    1909,  p. 

735  ff. 


NOTES    AM)    REFERENCES  213 

29.  Meltzer:  Lectures  on  G^clema.  American  JNleclicine,  1904,  1,  2,  4,  and  5. 

Starling:  Lectures.  Lancet,  190G,  May  9,  16,  23.  See  also:  Adami, 
Principles  of  Pathology,  ii,  p.  103  ff. 

30.  Archiv  fiirexperimentelle  Pathologic,  etc.,  42. 

31.  Important  in  this  connection  are  the  observations  made  in  experimental 

nephritis  induced  with  chromium  and  uranium  salts.  Chromium 
and  uranium  both  produce  a  nephritis,  which,  however,  in  the  former 
is  unaccompanied  by  cedema,  while  the  latter  is  associated  with  ex- 
tensive oedema.  Heineke,  moreover,  has  found  that  the  serum  of 
animals  poisoned  with  uranium  has  the  property  of  producing  oedema 
in  other  animals.  Similarly,  it  has  been  shown  by  Kast  and  Starling 
that  the  blood-serum  of  oedematous  nephritics  causes  increased  lymph- 
flow  in  animals.  See  also,  Pearce,  Archives  of  Internal  Medicine, 
iii,  1909,  p.  422. 

32.  Die  Gewebespannung.     Leipzig,  1884, 

33.  Krehl,  loc.  cit.,  p.  123,  with  further  literature. 


APPENDIX 


Classification  of  Nephritis 

I.  Xephritis  simplex:  Cloudy  swelling,  inflammatory  oedema,  and  serous 
exudate. 

Nephritis  prolijera:    Characterized  particularly  by  inflammatory  pro- 
liferation of  parenchyma  cells. 

II.  Xephritis  degenerativa  et  exudativa:  Marked  degenerations  and  necrosis 
of  fixed  cells,  and  cellular  exudate  into  glomeruli,  periglomerular  and 
intertubular  tissue.  Inflammatory  proliferation  of  epithelium. 
Cast  formation.  Frequenth^  hemorrhages  and  proliferation  of  fixed 
cells. 

III.  Xephritis  degenerativa  et  productiva:    The    exudative  features    in  the 

background.  The  degenerative  (particularly  fattjO  changes  promi- 
nent; cast  formation;  proliferation  of  epithelium  and  formation  of 
epithelial  giant-cells;  gradual  collapse  and  loss  of  kidnej^  sub- 
stance; appearance  of  leukocytoid  and  fibroblastic  cells  in  the  in- 
terstitial tissue,  with  the  gradual  formation  of  mature  fibrous  tissue, 
first  patchy,  then  more  diffuse.  Hemorrhages  occasionally  present. 
Gradual  thickening  of  blood-vessels,  with  occasional  infarcts. 

IV.  Xephritis  productiva:    Gradual,   first  patchy,   then  more  diffuse,   in- 

flammatory obliteration  of  renal  parenchyma,  leading  to  general, 
particularly'  cortical,  loss  of  kidney  substance.  Abundant  over- 
growth of  fibrous  connective  tissue.  Gradual  change  in  the  tj^pes 
of  secretory  epithelium.  Marked  thickening  of  blood-vessels,  with 
eventual  narrowing  of  lumen  and  obliteration.  As  the  result  of 
these,  infarct  formation  with  healing  b}'  scar  tissue. 

XOX-IXFLAMMATORY  LeSIONS  OF  THE  KiDNEY,  OCCASIONALLY,  BUT  WrONGLY, 

Grouped  as  Nephritis 

I.  Induratio  cyanotica  renum:  The  cyanotic  induration  of  the  kidnej's  re- 
sulting from  nutritive  disturbances  as  the  result  of  long-continued 
venous  stasis.  Congestion  of  all  vascular  districts,  taking  origin 
and  remaining  marked  particularl}'  in  the  medulla;   accentuation  of 

214 


APPENDIX  215 

all  iiiaikinjij.s  followcil  hy  (jedematou.s  iinhilntioii  uf  the  parts;  lucal- 
izcd  atropliy  and  collapse  of  kidney  substance  with  equally  localized 
fibrous  tissue  growth.  Secondary  changes  in  blood-pigment,  due 
to  hemolysis  and  setting  free  of  clumps  of  blood-pigment. 

II.  Alrnplud  vel  sclerosis  remnn:  The  senile  atrophy  and  sclerosis  of  the 
kidney.  Slight  and  patchy,  to  extreme  and  general  atrophy  and 
obliteration  of  renal  parenchyma,  with  marked  arteriosclerosis, 
obliteration  of  vessels,  and  infarctions.  Dilatation  of  renal  pelvis 
with  marked  })reaking  up  or  loss  of  its  elastic  muscular  layer.  Fre- 
quently additional  .stasis  with  oedema.  In  certain  cases  the  arterio- 
sclerotic changes  much  le.ss  prominent,  infarctions,  therefore,  lacking, 
and  the  kidney  presents  a  simple  diminution  in  size,  with  relatively 
smooth  surface. 


INDEX  TO  AUTHORS 


Adami,  57,  122,  173 

Mt'ms,  4 

Albrecht,  57,  5S,  123 

Altmann,  52 

Arnold,  60 

Aschoff,  14,  64,  123,  124,  178,  179 

Asher,  39 

Aufrecht,  112 

Avicenna,  5 


Cotugno,  5 
Councilman,  l.S,  107 
Cruikshank,  5 
Cushny,  33,  39 


Delafield,  24 
Desir,  S 
Dreser,  33,  34 


Bamberger,  184 

Bang,  119 

Bartels,  16,  18,  163,  178,  195 

Bauer,  116 

Baum,  148,  168 

Baumgarten,  60,  109 

Beck,  188 

Becquerel,  9 

Beer,  14,  22,  60 

Benario,  55 

Beneke,  120 

Bertini,  28 

Biermer,  18 

Birch-Hirschfeld,  56 

Bossard,  122 

Bowman,  10,  14,  29,  31 

Boyd,  33 

Brand  e,  5 

Bright,  5,  6,  7,  16,  162,  163,  183,  185,  188, 

193 
Brodie,  41 
Busk,  10,  11,  162 
Butschli,  123 


Canst  ATT,  10 

Christison,  7,  8,  16,  162,  193 

Cohnheim,  14,  15,  16,  22,  56,  178,  185,  186, 

187,  190,  191,  192,  194,  195,  196,  197 
Copland,  8 


Edebohls,  154 
Ehrlich,  180 
EUiotson,  8 
Engel,  133 
Ernst,  102 
Ewald,  170,  188 


Fahr,  169,  170,  175 
Fischler,  117 
Frerichs,  7,  11,  162 
Friedeman,  170,  173 
Friedlander,  67,  93 


Galeotti,  57 

Genest,  S 

Gluge,  9,  10 

Goethe,  200 

Golgi,  60 

Goodsir,  14 

Gottlieb,  39,  40 

Graves,  8 

Gregory,  7 

Gull,  16,  163,  176,  188 


Hall,  154 
Hasenfeld,  184 
Hausmann,  39 


21^ 


218 


INDEX 


Hecht,  9 

Heidenhain,  35,  36,  37 

Heineke,  45,  46,  47,  60,  99 

Henle,  10,  28,  30,  100,  102,  162 

Herring,  30 

Herxheimer,  134,  147,  148,  154 

Heubner,  111 

Hirsch,  184,  188 

Hofman,  116 

Horn,  160 

Hueter,  134 


Israel,  102,  191 


Janeway,  190 
Johnson,  10,  11,  16,  162 
Jores,  169,  170 


Katzenstein,  191 

Kaufman,  59 

Klebs,  15,  18,  56,  67,  102 

Kletzinski,  118 

Klotz,  122 

Koranyi,  40 

Kraus,  123 

Krehl,  184,  187,  190,  196 


Laxderer,  196 

Landsteiner,  56,  57,  101 

Langhans,  103 

Lebedeff,  116 

Leyden,  7, 16 

Lichtheim,  186,  195,  196 

Liebreich,  121 

Litten,  103 

Lohlein,  20,  21,  45,  107,  111,  121,  133,  163 

Lowi,  39 

Lubarsch,  64,  102 

Ludwig,  31,  32,  34,  35,  36,  39,  40,  41,  186, 

191 
Lusk,  116,  117 
Lyon,  93,  99,  102,  103 


Magnus,  39,  196 
Mann,  111 


Marchand,  20,  45,  46,  47,  64,  163,  170,  175 

Martland,  134 

Meltzer,  194 

Meyer  (Erich),  39,  40 

Meyer  (Hans),  33,  39 

Milne,  134,  149 

Morgagni,  5 

MlUler,  20,  24,  34,  41,  45,  47,  111,  150,  163, 

184 
Munk,  37 


N^GELI,  57 

Nasse,  10 

Nauwerck,  18,  64,  67,  178 

Niemann,  13 


Orgler,  57 
Orth,  18,  59,  101 
Osborne,  7 
Oswald,  125 
Overton,  118 


Panzer,  121 
Passler,  184 
Peris,  101 
Pettenkofer,  116 
Pfanndler,  39 
Pflliger,  116 
Ponfick,  134,  151 
Prvm,  169 


Ranson,  121 

Rayer,  8,  9 

Reinhardt,  7,  11,  15,  16,  162 

Ribbert,  15,  33,  67,  93,  94,  101,  103 

Rindfleisch,  56,  170,  173 

Rockitansky,  11 

Romberg,  184 

Rosenfeld,  116,  117,  122,  125 

Rosenstein,  15,  16 

Rosenthal,  122 

Roth,  170 

Rovida,  10,  100 

Roy,  37 

Rubow,  124,  125 

Rumpf,  116 


IxNDEX 


219 


Sahatiku,  S 

Schcrer,  10 

Schilling,  56 

Schrimus,  100 

Schmidt,  187 

SchmoU,  122 

Scudamore,  5 

Senator,  16,  IS,  10,  20,  iJo,  'M ,  (Ci,  15.5,  KW, 

IS.-),  1S7,  ISS,  ISO,  100,  10.5,  106,  107 
Sicbold.  10 
Simon,  10,  162 
Solon,  0 
Starling,  194 
Stewart,  16,  163 
Steyrer,  39 
Sutton,  16,  163,  176,  188 


Taine,  -1 

Thelcmann,  1.54 

Thoma,  .56,  167,  170,  191 

Thudichum,  110 

Tissot,  S 

Toynbec,  10,  11,  162 

Traubc,  15,  1.55,  184,  185,  186,  187,  191,  192 


Valentin,  0 

van  C(jtt,  1.54 

van  t'HotT,  .33 

\'('r\vorn,  5S 

Virchow,  11,  12,  13,  14,  15,  16,  17,  22,  .52, 

55,  56,  59,  60,  64,  66,  115,  117,  US,  123, 

179 
Vogcl,  10,  12 
von  Han.seniann,  126 
von  Kahldon,  64,  85,  86 
von  Recklinghausen,  56 
von  Voit,  116 


Wagner,  18 

Weigert,  14,  17,  18,  20,  23,  60,  64,  102,  153, 

162,  178,  179,  180,  181 
Weissgerber.  101 
Wells,  5 
\Mchman,  134 
Wilks,  16,  163 
Willis,  8 


ZiEGLER,  18,  56,  66,  133,  163 


INDEX 


Aci'TE  interstitial  iipphritis,  views  on,  IS 
parenchymatous  degeneration,  45 
use  of  word,  23 
Alhrceht's  views  on  protoplasm,  57 
Albuminuria,  first  demonstration,  5 
in  fatty  stage,  157 
in  productive  nephritis,  1S3 
in  simple  nephritis,  59 
nephritic,  urinary  quotient  in,  41 
orthostatic,  urinary  quotient  in,  41 
physiologic,  urinarj'  quotient  in,  41 
Solon's  views,  9 
Alkalinity   of   plasma,   diminution   of,   124, 

125 
Altmann's  granules  in  parenchymatous  de- 
generation, 52 
Amyloid  deposits,  134 
Anasarca,  193,  194 
Arsenic,  oedema  from,  196 
Arteries  in  productive  nephritis,  167,  169 
Arteriocapillary  fibrosis,  163,  188 
Arteriosclerosis  in  productive  nephritis,  169 

splanchnic,  blood-pressure  and,  188 
Arteriosclerotic  kidney,  174 
Asher's  theory  of  urine  secretion,  39 
Atherosclerosis  in  productive  nephritis,  169 
Atrophia,  25 
renum,  174 

vcl  sclerosis  renum,  215 
Atrophy  of  glomeruli,  133,  151 
Autolysis,  granular  degeneration  and,  57 
Autolytic  processes.  114,  118,  124 


l^KRTixi,  columns  of,  28 
Bibliography  of  fifth  lecture.  211 

of  first  lecture,  201 

of  fourth  lecture,  209 

of  second  lecture,  205 

of  third  lecture,  207 
liladder,  discharge  of  urine  into,  43 


Hlood  in  urine,  first  demonstration,  5 

water  in,  urine  secretion  and,  32 
Blood-pressure,  183 

suprarenal  glands  and,  192 

urine  secretion  and,  31 
Blood-supply  of  kidney,  28 
Blood-vessels,  crdema  from  injury  to,  196 
Bowman's  capsule,  29 

theory  of  urine  secretion,  31 
Bright's  disease,  lesions  included,  3 

observations,  6,  7 
Busk's  views,  11 


Canstatt's  views,  10 
Capillaries  in  productive  nephritis,  173 
Capillary  endothelium,  proliferation  of,  86 
Capsular   connective-tissue,  glomerular   re- 
placement, 147 
Capsule,  Bowman's,  29 

epithelium  of,  prohferation,  86 

in  degenerative  nephritis,  68 

in  exudative  nephritis,  68 

in  simple  nephritis,  48 

of  kidney,  epithelium  of,  30 
Casts  in  productive  nephritis,  183 
Catarrhal  inflammation,  definition,   13 
Cellular  casts,  100 
Cerebrosides,  chemistry  of,  120 
Cessation  of  symptoms,  113 
Characteristics  of  inflammation,  3 
Chemical  causes  of  oedema,  198 

theory  of  blood-pressure,  184 
Cholera,  kidney  in,  45 
Cholesterin,  118 

chemistry  of,  120 
Cholesterin-ester-fat  infiltration,  124 
Cholin,  119 
Chromatin  masses,  94 
Chromium  poisoning,  kidney  in,  45 
Chronic,  use  of  word,  23 


221 


222 


INDEX 


Classification,  1.  3,  4,  24,  6-5,  214 
Cloudj'  swelling,  52 
origin,  55 
significance,  55 
Colloid  bodies,  114 
Columns  of  Bertini,  28 

Concentric   cardiac   hj-pertrophy   in   neph- 
ritis, 185 
Connective-tissue  changes,  107 
in  fatty  degeneration,  134 
Contracted  kidney,  161,  162 

secondary.     111,    112,    152.      See  also 
Secondary  contracted  kidney. 
Corrosive  sublimate  poisoning,  kidney  in, 

45,  46,  60 
Cortex  in  degenerative  nephritis,  68 
in  exudative  nephritis,  68 
in  simple  nephritis,  48 
of  kidne3\  27 
Crescent  pictures,  86 
Croupous  inflammation,  definition,  13 
Cryoscopy  of  urine,  33 
Cyanotic  induration  in  nephritis,  159 
Cylindroids,  103 
Cysts  in  productive  nephritis,  168 


Decapsulation,  154 
Degeneration,  granular,  52,  53 
origin,  55,  57 
significance,  55,  57 
parenchymatous,  64 
acute,  45 

in  simple  nephritis,  52 
microscopic  appearances,  52 
without  inflammation,  45 
Degenerative  exudative  nephritis,  63 
cessation  of  symptoms,  113 
fatty  changes,  114 
functional  changes,  108 
gross  appearances,  68 
histogenesis,  63 
microscopic  appearances,  85 
nutritional  changes,  114 
oedema  in,  189 
pathogenesis,  63 
profluctive  changes  in,  110 
prognosis,  1 10 
related  kidney  changes,  158 
results,  110 


Degenerative  exudative  nephritis,  termina- 
tions, 110 
urine  in,  108 
fatty  nephritis,  115 
features,  45 
nephritis,  63 
causes,  67 

gross  appearances,  68 
histogenesis,  63 
pathogenesis,  63 
Diabetes  insipidus,  urine  of,  40 
Diagnosis,  early,  112 

in  venous  stasis,  155 
Di-amido-mono-phosphatides,  chemistry  of, 

119 
Diseases,  changing  character  of,  3 

included,  21 
Distearyl-lecithin,  120 
Dropsy,  kidney  changes  and,  5,  6 

liver  changes  and,  6 
Drugs,  oedema  from,  196 


Eccentric   cardiac  hypertrophy  in   neph- 
ritis, 185 
Endarteritis  fibrosa  in  productive  nephritis, 

170 
Endothelial  cells,  changes  in,  107 
Endothelium,  capillary,  proliferation  of,  86 
Enlargement  of  kidney,  115 
Epithelial  giant-cells  in  nephritis,  60 
Epithehum  in  fatty  degeneration,  149 

in  simple  nephritis,  51 

of  capsule  of  kidney,  30 
proliferation,  86 

of  glomeruli,  29 

of  loops  of  Henle,  30 

of  tubules,  29 

cells  derived  from,  99 
newly  formed,  149 
prolifcn'ation,  94 

of  tuft,  i)rolif ('ration  of,  86 
Extrarenal  symptoms,  199 
Exudate,  constituents  of,  107 

in  simple  nephritis,  51 

origin,  107 
Exudative  features,  45 

nephritis.       S(!e     Degenerative     exudative 
'nepJiritis. 


INDEX 


223 


I'"at-i)U()1's,  107 

Fatty  (IcKciuTation,  114,  115 

distribution  of  fat,  120 

functional  changes,  l')(),  1")() 

glomeruli  in,  120 

glycogen  content  and,  117 

interlobular  tissue  in,  151 

of  heart,  fat  percentage,  124 

tubules  in,  14S 

vascular  apparatus  in,  151^ 
infiltration,  114,  11.') 

cholesterin-ester,  !_'  1 

distribution  of  fat,  Tiii 

functional  changes,  150,  150 

glomeruli  in,  126 

glycerin-ester,  124 

interlobular  tissue  in,  151 

tubules  in,  14.S 

vascular  apparatus  in,  153 
metamorphosis,  123 
nephritis,  degenerative,  115 
regeneration,  117 
substances,  demonstratiuu  of,  122 

in  degenerative  exudative  nephritis,  94, 
107 

origin,  115 

significance,  115 
Fever  urine  in  simple  nephritis,  59 
Fibrosis,  arteriocapillary,  103,  188 
Fibrous    tissue    proliferation    antl    paren- 
chymatous loss,  162,  178 
Fifth  lecture,  101 

bibliography  of,  211 
Filtration  theory  of  urine  secretion,  31 

objections  to,  34 
First  lecture,  1 

bibliography,  201 
Fluid  fat,  emulsification  of,  123 
Forms  of  Bright 's  disease,  7 
Fourth  lecture,  110 

bibliography  of,  209 
Freezing-point  of  urine,  33 
P'rerich's  views,  11 

Frictional  theory  of  high  blood-pressure,  1S8 
Functions    of    kidney,  pathological    varia- 
tions and,  27 

views  on,  27 


Giant-cells  in  nephritis,  00 


( ilomcruli,  2s 

alteration  in  size,  148 

«-tTectson,  110,  HI 

epithelial  lining  of.  29 

formation,  28 

in  degenerative  nephritis,  68,  85 

in  fatty  degeneration,  120 

in  productive  nephritis,  100,  107 

in  simple  nephritis,  48,  51 
(jlomerulo-nepliritis,  19,  21,  00,  07 

l)ro(luctivc,  1 12 
Glycerin  phosphoric  acid  in  urine,  120 
Glycerin-ester-fat  infiltration,   124 
Glycogen   content,  fatty  degeneration  and, 

117 
Granular  casts,  100 

degeneration,  52,  53 
origin,  55,  57 
significance,  55,  57 


Halb.moxd  j)icturcs,  SO 
Heart,  fatty  degenerated,  fat  percentage  in, 
124 

hypertrophy  of,  in  nephritis,  184 

in  nephritis,  183 
Heidenhain's  theory  of  urine  secretion,  35 
Hematuria,  first  demonstration,  5 
Hemorrhages    in     tlegenerative    exudative 

nephritis,  85,  93 
Hemorrhagic  nephritis,  153 
Henle,  loops  of,  28 
ejMtheluim  of,  30 

views,  10 
Hippuric    ac-id  from  glycocoll  and  benzoic 

acid  in  kidney,  35 
Histological  investigations,  9 
Histology  of  kidney,  27 
Historical  review,  1,  21,  41 
Hyahne  bodies,  114 

casts,  100 

constitution,  100,  101 

thrombi,  93 

transformation,  133,  134,  147 
HydruMuia,  197 

Hydra>mic  plethora,  (edema  and,  195 
Hydronephrosis  in  senile  kidney,  177 
Hydrops,  193 

irritations,  190,  197 


224 


INDEX 


Hyperseniia,  active,   nitrogen  excretion  in, 
37 
sodium  chlorid  excretion  in,  37,  38 
urine  secretion  in,  37 
in  degenerative  exudative  nephritis,  104 
oedema  and,  194,  195 
Hypercompensation,  180 
Hypertrophy,  causes,  56 

of  coats  of  arteries  in  productive  neph- 
ritis, 173 
of  glomeruli,  148 
of  heart  in  nephritis,  184 
of  tubules,  150 


Indigo  carmin  injections  into  renal  artery, 

where  found  after,  35,  36 
Induratio  cyanotica  renum,  214 
Infarcts,  176 
Inflammation,  characteristics  of,  3 

conception  of,  3,  63 

definition,  12 
Inflammatory  processes,  interstitial  changes 

in,  180 
Interlobar  artery,  28 
Interlobular  arteries,  28 

tissue  in  fatty  stage,  151 
Internal  resistance  within  renal  circulation, 

191 
Interstitial    and    parenchymatous    forms, 
discussion,  14 

connective  tissue,  14 

hyperplasias,  early  work,  14 

nephritis,  chronic,  161.     See  also  Produc- 
tive nephritis. 
primary,  163 
views  on,  18 

tissue,  changes  in,  104 

use  of  term,  22 
Isocholesterin,  121 


Kaprosterin,  121 

Kephahn,  119 

Kidney,  anatomical  changes,  2 

anatomy  of,  28 

arteriosclerotic,  174 
as  filter,  31 

blood-supply  of,  28 

capsule  of,  epithelium  of,  30 


Kidney  changes,  8 
contracted,  161,  162 

cyanotic,  159 

red,  163 

secondary.  111,  112,  152 

productive  nephritis  and,  relations, 
162 
cortex  of,  27 
disease,  difficulties  of  studying,  1 

historical  review,  4 

included  under  Bright's  disease,  21 

structural  and  functional  changes,  re- 
lationship, 2 
enlargement  of,  115 
functions  of,  2 

pathological  variations  and,  27 

views  on,  27 
glomeruli  of,  28 

epithelial  lining  of,  29 

formation,  28 
hippuric  acid  formation  in,  35 
histological  changes,  2 
histology,  27 
in  cholera,  45 
in  chromium  poisoning,  45 
in  corrosive  sublimate  poisoning,  45,  46, 

60 
in  phosphorus-poisoning,  45,  116 
in  simple  nephritis,  47,  48 
inner  part,  27 
large  white,  115,  153 
lymphatics  of,  29 
medulla  of,  27 

extirpation  of,  urine  secretion  after,  39 
medullary  rays  of,  28 
nerves  of,  29 
outer  part,  27 

pathologic,  different  from  normal,  44 
pelvis  of,  discharge  of  urine  from,  43 

in  senile  kidney,  177 

structure,  43 
productive  changes  in,  110 
pyramids  of,  28 
senile,  174 
structure,  27 

synthetic  processes  in,  35 
tubercles  in,  formation,  60 
tubules  of,  28 

epithelial  lining  of,  29,  30 

Ludwig's  theory  of  function  of,  32,  33 


INDEX 


225 


KidiK'v,  urinary  clirumogons  in,  35 

vascular   apparatus   of,    in  fattj'    stage, 
153 

Ivoranyi's  theory  of  urine  secretion,  40 
urinary  quotient,  40 


Large  white  kidney,  llo,  153 
Lecithin,  118,  119 
Lipoids,  lis,  119 
Lohlein's  views,  20 
Loops  of  Henle,  28 

epithelium  of,  30 
Ludwig's  theory  of  function  of  tubules,  32, 
33. 

of  urine  secretion,  31,  34 
Lymphangitis  in  nephritis,  107,  194 
Lymphatic  changes,  oedema  and,  196,  197 
Lymphatics  of  kidney,  29 


Mechanical  causes  of  cardiac  hypertrophy, 
186 

Medulla,  27 

extirpation  of,  urine  secretion  after,  39 
in  degenerative  exudative  nephritis,  68 
in  simple  nephritis,  48 

Medullary  rays  of  kidney,  28 

^leninges  in  nephritis,  193 

Mej'er's  views  on  urine  secretion,  40 

Mono-amido-di-phosphatides,  chemistrj-  of, 
119 

Mono-amido-mono-phosphat  ides,      chemis- 
try of,  119 

Miiller's  views,  20 

■Munk  and  Senator's  theory  of  urine  secre- 
tion, 37 

Mvelins,  118,  119 


Nephritis  degcnerativa,  25 
adiposa,  25 
et  exudativa.  63 
exudativa,  25 
hajmorrhagica,  25 

prolifera,  25,  59,  61.     See  also  Prolifera- 
tive nephritis. 
et  productiva,  59,  61.     See  also  Pro- 
liferative nephritis. 
simplex,  24 
16 


Nephropathia  chronica  inflammatoria,  179 

Nephroses,  45 

Nerves  of  kidney,  29 

Nitrogen  excretion  in  hyperaemia,  37 

in  stasis,  37 
Non-inflanmiatory  processes,  3 

wrongly  grouped  as  nephritis,  214 
Nutritional  changes,  114 


(EDE.MA,  161,  183,  189,  193 

in  degenerative  exudative  nephritis,  104, 
189 

irritation,  197 
Oleyl-lecithin,  120 
Orth's  \-iews,  18 
Osmotic  pressure  of  urine,  33 


Palmityl-lecithix,  120 
Paramyelin,  chemistry  of,  119 
Parenchymatous  and  interstitial  forms,  dis- 
cussion, 14 
degeneration,  64 
acute,  45 

in  simple  nephritis,  52 
microscopic  appearances,  52 
inflammation,  definition,  13 

Virchow's  %'iews,  12 
nepliritis,  a^dema  in,  189 
use  of  term,  22 
Pathological  processes,  changing  character 

of,  3 
Peh-is  of  kidne\',  discharge  of  urine  from, 
43 
in  senile  kidney,  177 
structure,  43 
Pericardium  in  nephritis,  193 
Perilymphangitis  in  nephritis,  107,  194 
Peritoneum  in  nephritis,  193 
Pfister.  101 

Phosphatides,  chemistry  of,  119 
Phosphoric  acid,  glycerin,  in  urine,  120 
Phosphorus-poisoning,  kidney  in,  45,  116 
Phrenosin,  121 

Phytosterin,  chemistry  of,  120 
Plasma,  alkaUnity  of,  diminished,  124.  125 
Pleura  in  nephritis,  193 
Productive  changes  in  kidnej",  110 
nephritis,  25,  161 


226 


INDEX 


Productive  nephritis,  albuniinuria  in,  183 

arteries  in,  167,  169 

arteriosclerosis  in,  169,  174 

atherosclerosis  in,  169 

capillaries  in,  173 

cardiac  hypertrophy  in,  1S9 

casts  in,  183 

causes,  165 

circulation  in,  167,  169 

cysts  in,  168 

endarteritis  fibrosa  in,  170 

fibrous  tissue  prohferation  in,  162,  178 

functional  changes,  167,  181 

glomeruh  in,  166,  167 

gross  appearances,  161 

hypertrophy  of  coats  of  arteries  in,  173 

microscopic  appearances,  165 

parenchymatous  loss  in,  162,  178 

secondary  contracted  kidney  and,  re- 
lations, 162 

tubules  in,  166 

urine  in,  181 

vascular  changes,  167,  169 
Prognosis,  110 

Proliferation  in  fatty  degeneration,  149 
of  epithelium,  86 

of  tubules,  94 
Proliferative  nephritis,  25,  59,  61 

functional  changes,  63 

urine  in,  63 
Protagon,  118,  120,  121 
Protoplasm,  views  on,  57 
Pyknosis,  94 
Pyramids  of  kidney,  28 


Payer's  views,  9 

Recoverj',  110,  111 

Picd  kidney,  small,  163 

Reflex  theory  of  cardiac  hypertrophy,  187 

Regeneration,  fatty,  117 

Reinhart's  views,  11 

Renal  artery,  28 

injections  of  indigo  carmin  into,  where 
found  after,  35,  36 

diarrhea,  39 

symptoms,  199 
Pir'pair  in  inflammatory  processes,  ISO 
]{ockitan.sky's  views,  11 


Scarlatinal  nephritis,  196 
Sclerosis,  174 
renum,  25 
Second  lecture,  27 

bibliography  of,  205 
Secondary  contracted  kidney.  111,  112,  152 
anatomical  evidences,  21 
productive  nephritis  and,  relations, 
162 
Secretion  casts,  101 
Senator's  views,  19 

theory  of  cardiac  hypertrophy,  189 
Senator  and  Munk's  theory  of  urine  secre- 
tion, 37 
Senile  kidney,  174 
pelvis  in,  177 
Serous  membranes  in  nephritis,  193 
Serum-albumin  in  urine.    See  Albuminuria. 
Simple  nephritis,  45,  47 
albuminuria  in,  59 
epithelium  in,  51 
exudate  in,  51 
fever  urine  in,  59 
functional  changes,  59 
glomeruli  in,  48,  51 
microscopic    appearances    of    kidney, 

51 
parenchymatous  degeneration  in,  52 
pathologic  histology,  47,  48 
termination,  58 
tissue  between  tubules  in,  58 
tubules  in,  52 
urine  in,  59 
Sodium  chlorid  and  water  resorption,   32, 
39 
excretion  in  hypersemia,  37,  38 
oedema  and,  197 
Solon's  views,  9 

Sphyngomyelin,  chemistry  of,  119 
Splanchnic   arteriosclerosis,    blood-pressure 

and,  188 
Stages  of  disease,  Bright's  views,  6,  7 
Staining  aflSnities  of  tube-casts,  102 
Stasis,  nitrogen  excretion  in,  37 

urine  secretion  in,  37 
Sulphate  injections  into  blood,   urine  after, 

39 
Suprarenal  glands,  blood-jircssure  and,  192 
Symptoms,  199 
Synthetic  processes  in  kidney,  35 


INDEX 


227 


'liiiKD  liM'turc,  4") 

l)il)li<)Krai)hy  of,  207 
Tlirunihi,  hyaline,  \)'.i 
Tissue  botwoen  tubulos,  chiuifics  in,  104 
in  fatty  stapo,  151 
in  simple  nejjhritis,  58 
Toxie  theory  of  hifih  hlood-prcssurc,  ISS 
Toynbee'.s  views,  1 1 
Transudate  easts,  101 

use  of  term,  197 
Transudat ion-secretory  theory  of  urine  se- 

eretion,  3S 
Tri-amido-phosphatidc,  1 19 
Tropfip;e  entmisehuufi,  57,  5S,  123 
Tube-easts,  100 

eellular,  100 

composition,  100 

firanular,  100 

iiyaline,  100 

constitution,  100,  101 

secretion,  101 

staining  affinities,  102 

transudate,  101 

waxy,  100 

constitution,  100,  102 
Tubercles  in  kidney,  formation,  60 
Tubules,  2S, 

ililatation  of,  100 

effects  on,  1 1 1 

enlargement  of,  150 

epithelium  of,  29,  30 
cells  derived  from,  99 
newly  formed,  149 
jjroliferation,  94 

in  degenerative  exudative  nejihritis,  93 

in  fatty  degeneration,  14S 

in  productive  nephritis,  166 

in  simple  nephritis,  52 

Ludwig's  theory  of  function  of,  32,  33 
Tuft,  appearances  of,  86 


Irine  examination,  early,  4 
fever,  in  simple  nephritis,  59 
freezing-point  of,  33 
glycerin  phosphoric  acid  in,  120 
in  degenerative  exudative  nephritis,  108 
in  fatty  stage,  156 
in  {)roductive  ncfjhritis,  181 
in  proliferative  nephritis,  ()3 
in  simple  nephritis,  59 
in  venous  stasis,  155,  158 
of  diabetes  insipidus,  40 
osmotic  i)ressure  of,  33 
secretion,  27 

after  extirpation  of  medulla,  39 

after  injections   into   blood  of  sodium 
sulphate,  39 

Asher's  theory,  39 

blood-pressure  and,  31 

Bowman's  theory,  31 

filter  theory,  31 

Heidenhain's  theory,  35 

in  hypera^mia,  37 

in  stasis,  37 

Koranjd's  theor}',  40 

Ludwig's  theory,  31,  34 

Meyer's  views,  40 

Senator  and  Munk's  theory,  37 

summary  of  views,  41 

transudation-secretory  theory,  38 

views  on,  31 

water  in  blood  and,  32 


Vas  efferens,  29 

Vascular  apparatus  in  fatty  stage,  153 

in  productive  nephritis,  167,  169 
Venous  stasis,  154,  197 
Virchow  on  parenchymatous  inflammation, 

12 
Visceral  changes,  161,  183 


I'kktkk,  discharge  of  urine  into,  43  Water  and  .sodium  chlorid  resorption,  32, 

structure  of,  43  39 

I'rinary  chromogens,  formation  in  kidney,  resorption,  42 

35  by  tubules,  32,  33 

quotient,  40  Waxy  casts,  100 

Urine,  cryoscopy  of,  33  constitution,  100,  102 


discharge  from  pelvis,  43 


Weigert's  views,  17 


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